Bee virus spread manmade and emanates from Europe

Public Release: 4-Feb-2016

 

The spread of a disease that is decimating global bee populations is manmade, and driven by European honeybee populations, new research has concluded

University of Exeter

The spread of a disease that is decimating global bee populations is manmade, and driven by European honeybee populations, new research has concluded.

A study led by the University of Exeter and UC Berkeley and published in the journal Science found that the European honeybee Apis mellifera is overwhelmingly the source of cases of the Deformed Wing Virus infecting hives worldwide. The finding suggests that the pandemic is manmade rather than naturally occurring, with human trade and transportation of bees for crop pollination driving the spread.

Although separately they are not major threats to bee populations, when the Varroa mite carries the disease, the combination is deadly, and has wiped out millions of honeybees over recent decades. Varroa feed on bee larvae while the Deformed Wing Virus kills off bees, a devastating double blow to colonies. The situation is adding to fears over the future of global bee populations, with major implications for biodiversity, agricultural biosecurity, global economies, and human health.

The study was funded by the Natural Environment Research Council (NERC) and supported by a Royal Society Dorothy Hodgkin Fellowship. It involved collaborators from the universities of Sheffield, Cambridge, Salford and California, as well as ETH Zurich in Switzerland.

Lead author Dr Lena Wilfert, of the University of Exeter’s Centre for Ecology and Conservation, on the Penryn Campus in Cornwall, said: “This is the first study to conclude that Europe is the backbone of the global spread of the bee killing combination of Deformed Wing Virus and Varroa. This demonstrates that the spread of this combination is largely manmade – if the spread was naturally occurring, we would expect to see transmission between countries that are close to each other, but we found that, for example, the New Zealand virus population originated in Europe. This significantly strengthens the theory that human transportation of bees is responsible for the spread of this devastating disease. We must now maintain strict limits on the movement of bees, whether they are known to carry Varroa or not. It’s also really important that beekeepers at all levels take steps to control Varroa in their hives, as this viral disease can also affect wild pollinators.”

Researchers analysed sequence data of Deformed Wing Virus samples across the globe from honeybees and Varroa mites, as well as the occurrence of Varroa. They used the information to reconstruct the spread of Deformed Wing Virus and found that the epidemic largely spread from Europe to North America, Australia and New Zealand. They found some two-way movement between Europe and Asia, but none between Asia and Australasia, despite their closer proximity. The team also looked at samples from other species suspected of transmitting the disease, including different species of honeybee, mite and bumblebees, but concluded that the European honeybee was the key transmitter.

Professor Roger Butlin, Professor of Evolutionary Biology at the University of Sheffield, said: “Our study has found that the deformed wing virus is a major threat to honeybee populations across the world and this epidemic has been driven by the trade and movement of honeybee colonies.

“Domesticated honeybee colonies are hugely important for our agriculture systems, but this study shows the risks of moving animals and plants around the world. The consequences can be devastating, both for domestic animals and for wildlife. The risk of introducing viruses or other pathogens is just one of many potential dangers.”

Senior author Professor Mike Boots of Exeter and UC Berkeley concluded: “The key insight of our work is that the global virus pandemic in honeybees is manmade not natural. It’s therefore within our hands to mitigate this and future disease problems.”

###

The report, “Deformed wing virus is a recent global epidemic in honeybees driven by Varroa mites”, is published in Science on Friday February 5, by L.Wilfert, G Long, H.C. Leggett, P Schmid-Hempel, R. Butlin, S.J.M Martin and M Boots.

About the University of Exeter

The University of Exeter is a Russell Group university that combines world-class research with very high levels of student satisfaction. Exeter has over 19,000 students and is one of the global top 100 universities according to the Times Higher Education World University Rankings 2015-16, positioned 93rd. Exeter is also ranked 7th in The Times and The Sunday Times Good University Guide 2016, 9th in the Guardian University Guide 2016 and 10th in The Complete University Guide 2016. In the 2014 Research Excellence Framework (REF), the University ranked 16th nationally, with 98% of its research rated as being of international quality. Exeter was named The Times and The Sunday Times Sports University of the Year 2015-16, in recognition of excellence in performance, education and research. Exeter was The Sunday Times University of the Year 2012-13.

The University has four campuses. The Streatham and St Luke’s campuses are in Exeter and there are two campuses in Cornwall, Penryn and Truro. In a pioneering arrangement in the UK, the Penryn Campus is jointly owned and managed with Falmouth University. At the campus, University of Exeter students can study programmes in the following areas: Animal Behaviour, Conservation Biology and Ecology, English, Environmental Science, Evolutionary Biology, Geography, Geology, History, Human Sciences, Marine Biology, Mining and Minerals Engineering, Politics and International Relations, Renewable Energy and Zoology.

The University has invested strategically to deliver more than £350 million worth of new facilities across its campuses in the past few years; including landmark new student services centres – the Forum in Exeter and The Exchange at Penryn – together with world-class new facilities for Biosciences, the Business School and the Environment and Sustainability Institute. There are plans for further investment between now and 2016. http://www.exeter.ac.uk/cornwall

Probable Bioweapon: Influenza Type A Virus – A Short Case Report.

clip_image002Journal of Bioterrorism & Biodefense

 

Abstract

Influenza type A virus (Influenza virus A), an old foe of mankind, is presently the most significant pathogen causing both pandemics and epizootics, worldwide. The proliferative husbandry of poultry and pigs, primarily, constitutes a key factor in ongoing generation of pandemic and pre-pandemic strains, which is fueled by remarkable wild aquatic bird permissiveness of the virus. Those attributes are here thoroughly inquired into, so as to profile and rate threat and usability. Also, various human interventions and misuses, including human experimental infections, undesirable vaccinations, as well as unauthorized and unskillful operations, led to bad corollaries and may rather be reassessed and modified or disallowed. Diversified interfaces between influenza and human manners are thereby brought out and elucidated, along with their lessons.

Introduction

Continue reading “Probable Bioweapon: Influenza Type A Virus – A Short Case Report.”

A VIRUS that kills every one of its victims, by wiping out part of their immune system, has been accidentally created by an Australian research team

Requested Re-post from our evesdrift.com site, on the horrifying potential of a certain type of disease vaccine engineering.

New Scientist issue: 13th January 2001 ( Historical )

An engineered mouse virus leaves us one step away from the ultimate bioweapon

A VIRUS that kills every one of its victims, by wiping out part of their immune system, has been accidentally created by an Australian research team. The virus, a modified mousepox, does not affect humans, but it is closely related to smallpox, raising fears that the technology could be used in biowarfare.

The discovery highlights a growing problem. How do you stop terrorists taking legitimate research and adapting it for their own nefarious purposes?

The Australian researchers had no intention of producing a killer virus. They were merely trying to make a mouse contraceptive vaccine for pest control. “But it’s a good way to show how to alter smallpox to make it more virulent,” says Ken Alibek, former second-in-command of the civilian branch of the Soviet germ-warfare programme.

Read More : evesdrift.com Continue reading “A VIRUS that kills every one of its victims, by wiping out part of their immune system, has been accidentally created by an Australian research team”

US Health Agency Holds Patent on Ebola Strain Virus

Sunday, 03 August 2014

The U.S. Centers for Disease Control owns a patent on a particular strain of Ebola known as “EboBun.” It’s patent No. CA2741523A1 and it was awarded in 2010. You can view it here.

Patent applicants are clearly described on the patent as including:

The Government Of The United States Of America As Represented By The Secretary, Department Of Health & Human Services, Center For Disease Control.

It goes on to state, “The present invention is based upon the isolation and identification of a new human Ebola virus species, EboBun. EboBun was isolated from the patients suffering from hemorrhagic fever in a recent outbreak in Uganda.”

 

It’s worth noting, by the way, that EboBun is not the same variant currently believed to be circulating in West Africa. Clearly, the CDC needs to expand its patent portfolio to include more strains, and that may very well be why American Ebola victims have been brought to the United States in the first place. Read more below and decide for yourself… Continue reading “US Health Agency Holds Patent on Ebola Strain Virus”

Experiments using virulent avian flu strains pose risk of accidental release

Experiments using virulent avian flu strains pose risk of accidental release //

PUBLIC RELEASE DATE:

20-May-2014

Research in mammals that aims to prevent future influenza pandemics raises ethical, public health concerns

Boston, MA — Experiments creating dangerous flu strains that are transmissible between mammals pose too great a risk to human life from potential release, according to an editorial by researchers from Harvard School of Public Health (HSPH) and Yale School of Public Health. The researchers are calling for greater scrutiny of experiments that make virulent influenza strains transmissible, and for future studies on flu transmission to use safer and more effective alternative approaches.

“These recent studies raise strong ethical questions,” said lead author Marc Lipsitch, professor of epidemiology and director of the Center for Communicable Disease Dynamics at HSPH. “We have accepted principles, embodied in the Nuremberg Code, that say that biomedical experiments posing a risk to human subjects should only be undertaken if they provide benefits that sufficiently offset the risks—and if there are no other means of obtaining those benefits. Although these experiments don’t involve people directly, they do put human life and well-being at risk.” Continue reading “Experiments using virulent avian flu strains pose risk of accidental release”

Live virus used in polio vaccine can evolve and infect, warns TAU researcher

” Can act like wild poliovirus and continue the threat of contagion ”  November 7, 2011 _ Requested Re-Post from our HRR Site

Health professionals and researchers across the globe believe they are on the verge of eradicating polio, a devastating virus which can lead to paralysis and death. Despite successful eradication in most countries, there are still four countries where the virus is considered endemic — and many more in which the virus still lurks.

Dr. Lester Shulman of Tel Aviv University’s Sackler Faculty of Medicine and the Israeli Ministry of Health has spent years tracking isolated cases of live poliovirus infections, often discovered in countries that are supposedly polio-free. When the live-virus version of the vaccine, called Oral Polio Vaccine (OPV) evolves, he says, it can act like wild poliovirus and continue the threat of contagion.

None - This image is in the public domain and ...

Continue reading “Live virus used in polio vaccine can evolve and infect, warns TAU researcher”

‘Alien’ life form is grown in a lab: Scientists add unnatural DNA strands to the genetic code of bacteria to create a new strain

 

  • Researchers at the Scripps Research Institute in La Jolla, California, introduced DNA molecules not found in nature to a common bacterium
  • The E. coli bugs are able to grow and reproduce as normal despite containing two extra letters in their genetic code
  • Research involved overcoming a billion years of evolution to get the expanded genetic alphabet into living bacteria
  • In the future the research could lead to creation of microbes capable of manufacturing entirely new proteins that could be used in medicine
  • Some people are worried that the rapid advance of ‘synthetic biology’ could lead to the worrying prospect of new life-forms escaping from labs

 

From left to right, the structures of A-, B- a...

Continue reading “‘Alien’ life form is grown in a lab: Scientists add unnatural DNA strands to the genetic code of bacteria to create a new strain”

France admits 2,300 samples of SARS virus are missing / They Claim Harmless

Thursday, 17 April 2014
A routine inventory at a Parisian research body revealed over 2,300 samples of the potentially deadly SARS virus are missing, The Independent reports.

 

The renowned Institute Pasteur in France admitted on Monday that it had misplaced 2,349 of the vials and, despite enlisting help from France’s drug and health safety agency, have been unable to find them. The investigation by the ANSM at the unnamed laboratory failed to locate the samples, which have been missing since January. It has now filed a case to the prosecutor of Paris to investigate the disappearance. Continue reading “France admits 2,300 samples of SARS virus are missing / They Claim Harmless”

Could dinosaur-age DNA cure GOUT? Reviving a 90 million-year-old protein could treat painful inflammation

  • Researchers have resurrected a prehistoric version of the enzyme uricase
  • Uricase can break down uric acid, which can cause kidney stones and gout
  • It is not produced in humans because of evolutionary changes that took place in the body over 20 million years ago

By Daily Mail Reporter

UPDATED:          08:05 EST, 21 February 2014

 

Resurrecting ancient DNA that was around when dinosaurs walked the Earth could help scientists find a cure for gout.

Researchers in Atlanta believe a 90 million-year-old version of an enzyme known as uricase could better treat the disease, which causes painful, swollen joints.

Gout is caused by the build-up of a chemical in the blood called uric acid, which is harmless to the body in small quantities.

Researchers in Atlanta believe a 90 million-year-old version of an enzyme known as uricase could better treat gout, which causes painful, swollen joints

Researchers in Atlanta believe a 90 million-year-old version of an enzyme known as uricase could better treat gout, which causes painful, swollen joints Continue reading “Could dinosaur-age DNA cure GOUT? Reviving a 90 million-year-old protein could treat painful inflammation”

Dosing schedule of pneumococcal vaccine linked with increased risk of getting multiresistant strain

Public release date: 7-Sep-2010 – EEV: Requested Re-Post from the HRR site.

Infants who received heptavalent pneumococcal conjugate vaccination (PCV-7) at 2, 4, and 11 months were more likely than unvaccinated controls to have nasopharyngeal acquisition of pneumococcal serotype 19A

– the increase in serotype 19A disease was associated in time with the widespread implementation of PCV-7 in routine infant immunization programs

– A rapid increase in the presence of pneumococcal serotype 19A strains that are often multiresistant to antibiotics has been observed over the last decade

– serotype 19A is now the leading causative pneumococcal serotype of invasive and respiratory pneumococcal disease

Question mark in Esbjerg
Question mark in Esbjerg (Photo credit: alexanderdrachmann)

Infants who received heptavalent pneumococcal conjugate vaccination (PCV-7) at 2, 4, and 11 months were more likely than unvaccinated controls to have nasopharyngeal (in the nasal passages and upper part of the throat behind the nose) acquisition of pneumococcal serotype 19A, a leading cause of respiratory pneumococcal disease, according to a study in the September 8 issue of JAMA. Continue reading “Dosing schedule of pneumococcal vaccine linked with increased risk of getting multiresistant strain”

Fun With Genetic Engineering: Why Letting Students Tinker With Microorganisms Is Good For Education And Society

Posted: 01/14/2014  1:26 pm

By Charles Gersbach, Assistant Professor, and Tom Katsouleas, Dean, Duke University’s Pratt School of Engineering

Elaborate competitions to build the best robot or design cages to protect falling eggs have been a rite of passage for generations of engineering students. Today, there’s a new contest with the same creativity and competitive spirit, but vastly more sophisticated projects–like mixing-and-matching bits of DNA to create new microorganisms that produce biofuels or costly medicines.

2014-01-14-bioeng.jpg

The International Genetically Engineered Machines (iGEM) competition challenges student teams to use cutting-edge tools from the new field of synthetic biology to design, build, and test genetically engineered organisms.  This fall, 133 teams of students from universities from around the world participated, producing an incredible array of projects.  Some engineered microorganisms to produce medicines, clean up environmental contaminants, or act as biosensors for toxins or other chemicals.  Others created genetically engineered living board games or transformed otherwise stinky bacteria to smell like wintergreen.  Our own Duke University iGEM team focused on engineering gene circuits in yeast to better understand how cells make decisions, such as whether to replicate or respond to an environmental stimulus; the circuits can also be used in biomanufacturing. Continue reading “Fun With Genetic Engineering: Why Letting Students Tinker With Microorganisms Is Good For Education And Society”

Bird flu leaves the nest — adapting to a new host ( How to Kill or Cure Millions )

EEV: Reposted at request from our biological site www.healthresearchreport.me

Public release date: 26-Aug-2009

– an unadapted avian strain and an avian strain adapted to infect mice by mutations that increase the efficiency of the viral polymerase

They found that whereas the avian strain only infected the lungs, the mouse-adapted strain caused suppression of the immune system, which resulted in infection in multiple organs

–  bird-specific flu strains rarely cross species, further adaption can lead to lethal infection in humans.

Hamburg, Germany – Current research suggests that viral polymerase may provide a new therapeutic target for host-adapted avian influenza. The related report by Gabriel et al, “Spread of Infection and Lymphocyte Depletion in Mice Depends on Polymerase of Influenza Virus” appears in the September 2009 issue of the American Journal of Pathology.

Highly pathogenic avian influenza, commonly known as bird flu, is a strain of the influenza virus that has adapted to infect birds. Although bird-specific flu strains rarely cross species, further adaption can lead to lethal infection in humans.

To determine which genetic changes may lead to host adaptation, Gülsah Gabriel (currently at the Heinrich-Pette-Institute for Experimental Virology and Immunology the University of Hamburg) and Hans-Dieter Klenk at the Institute of Virology at the Philipps University of Marburg examined two strains of avian influenza, an unadapted avian strain and an avian strain adapted to infect mice by mutations that increase the efficiency of the viral polymerase. They found that whereas the avian strain only infected the lungs, the mouse-adapted strain caused suppression of the immune system, which resulted in infection in multiple organs. In addition, while the avian strain caused only mild symptoms in mice, the mouse-adapted strain led to severe illness including pneumonia and infection of the brain, followed by death. The viral polymerase may therefore provide an important target in preventing systemic flu in humans.

Gabriel et al suggest that “reduction of high virus loads by targeting the viral polymerase may play an important role in the treatment of human influenza with systemic virus spread.” In future studies, Dr. Gabriel and colleagues will aim to develop drugs interfering with virus polymerase activity.

Scientists creating viruses deadlier to humans

Sunday, 22 December 2013

Some of the world’s most eminent scientists have severely criticised the arguments used by some influenza researchers who are trying to make the H5N1 bird-flu virus more dangerous to humans by repeatedly infecting laboratory ferrets.

More than 50 senior scientists from 14 countries, including three Nobel laureates and several fellows of the Royal Society, have written to the European Commission denouncing claims that the ferret experiments are necessary for the development of new flu vaccines and anti-viral drugs. Continue reading “Scientists creating viruses deadlier to humans”

Vaccine’s, the Lucky Rabbits Foot, and Shhh No questions allowed ( Part 1 )

Vaccines are just a form of medicine like everything else. Some of them good, and some of them not so good. In any case you have a right to know.

Just remember Scientific Method – Observation, Hypothesis, and Theory as well as Risk to Benefit Ratio ..> But don’t get me started on Epigenetics

We should all have the freedom to inoculate ourselves based upon fact… The first one However, I threw in for fun ; )

There are many more as this is just part 1 …. Just sticking with RECENT Peer Review. But let the first Salvo fly

Change in human social behavior in response to a common vaccine and Funvax Using Vaccines to Alter Human Behavior VMAT2 Gene 

Pneumococcal vaccination in adults does not appear to work

Live Vaccination against ( German Measles ) Rubella caused Signifigant Depression up to 10 weeks – Vaccines/ Bacteria Can Alter Mood and Behavior

No significant influenza (FLU) vaccine effectiveness could  be demonstrated for any season, age or setting after adjusting for county, sex, insurance, chronic conditions recommended for influenza vaccination and timing of influenza vaccination

The Hidden Threat That Could Prevent Polio’s Global Eradication – Vaccinated Children that Become  “chronic excreters”

U.S. Court Confrims M.M.R. Vaccine Caused Autism or Cumulative  (Verified through Multiple Sources) From DEC 2012 Judgment

Pig Virus DNA Found in Rotavirus Vaccine : Millions of children worldwide, including 1 million in the U.S. exposed

Seasonal flu vaccination increase the risk of infection with pandemic H1N1 flu by 68%

Flu vaccine may not protect seniors well / Vaccine was totally ineffective

OHSU research suggests America may over-vaccinate

Some children vaccinated against hepatitis B may have an increased risk of MS

Flu shot does not cut risk of death in elderly / no decrease in hospital admissions or all-cause mortality

Measles, Mumps, Rubella vaccine linked with 2-fold risk of seizures

‘MMR vaccine causes autism’ claim banned – Followed by 15 studies that link Strong Correlation, it May

Influenza Vaccine Failure among Highly Vaccinated Military Personal, No protection against Pandemic Strains.

Live virus used in polio vaccine can evolve and infect, warns TAU researcher

India: Paralysis cases soar after oral polio vaccine introduced

Flu Vaccine offers no Protection in seniors

Common cold virus can cause polio in mice when injected into muscles

Flu shot does not reduce risk of death

Swine flu vaccine linked to child narcolepsy: EU Confirmation

WHO and the pandemic flu “conspiracies” – FULL report from the BMJ and The Bureau of Investigative Journalism  2010

A vaccine-derived strain of poliovirus that has spread in recent years is serious but it can be tackled with an existing vaccine

Dosing schedule of pneumococcal vaccine linked with increased risk of getting multiresistant strain

Expert questions US public health agency advice on influenza vaccines

Whooping Cough Vaccine is obsolete ” Bulk of the cases were in fully vaccinated children ” few cases among unvaccinated children

Flu vaccine backfires in pigs / vaccinated against H1N2 influenza were more vulnerable to the rarer H1N1 strain

Higher anaphylaxis rates after HPV vaccination: CMAJ study / significantly higher – 5 to 20 fold – than that identified in comparable school-based vaccination programs

Allergic to Gummy Bears? Be Cautious Getting the Flu Shot

Vaccination campaign doubles HBV mutations

From friend to foe: How benign bacteria evolve to virulent pathogens

Contact: Isabel Gordo igordo@igc.gulbenkian.pt 351-214-407-915 Public Library of Science

Bacteria can evolve rapidly to adapt to environmental change. When the “environment” is the immune response of an infected host, this evolution can turn harmless bacteria into life-threatening pathogens. A study published on December 12 in PLOS Pathogens provides insight into how this happens.

Isabel Gordo and colleagues from the Instituto Gulbenkian de Ciencia in Oeira, Portugal, have for the first time devised an experimental system to observe and study the evolution of bacteria in response to encounters with cells of the mammalian immune system. They found that in less than 500 bacterial generations (or 30 days), the bacteria became more resistant to being killed by immune cells and acquired the ability to cause disease in mice. Continue reading “From friend to foe: How benign bacteria evolve to virulent pathogens”

Genomics pioneer Craig Venter warns about biohacker boo-boos (i.e. Doomsday Virus )

Alan Boyle, Science Editor         NBC News

Oct. 24, 2013 at 11:01 AM ET

Image: J. Craig Venter

Hyungwon Kang / Reuters file
Biologist J. Craig Venter testifies at a congressional hearing in 2010.

In his latest book, genetic guru J. Craig Venter envisions a brave new world where DNA can be teleported between planets and where custom-made bacteria produce drugs, food and biofuel — but he also worries that do-it-yourself biohackers could spoil that vision.

“One of the concerns that I  address in my book is this new emergence of do-it-at-home biology,” Venter told NBC News. “One important part of scientific training is that scientists learn the boundaries, the safety issues, how to properly deal with and dispose of chemicals and reagents.

“While it’s great at one level that there’s excitement and people wanting to do experiments at home, playing with things without the proper knowledge set and the proper training, I think, legitimately raises concerns for an increased chance of unintended consequences,” he said.

As Venter points out in his book, “Life at the Speed of Light,” he’s not the only one worried about biohacker boo-boos. Almost three years ago, a presidential commission on bioethics raised concerns about the risk of “low-probability, high-impact events” such as the creation of a doomsday virus. Bioterror is one aspect of the issue, but Venter says he’s also concerned about bio-error — “the fallout that could occur as the result of DNA manipulation by a non-scientifically trained biohacker or ‘biopunk.'”

Some have called for more regulation of synthetic biology and home biotech. Venter, however, says overregulation can be as harmful as laxness. It’s possible to add built-in safeguards — such as biological kill switches, suicide genes or molecular brakes and seatbelts — to make sure genetically engineered microbes don’t escape from the lab. And law-enforcement agencies like the FBI are finding it more advantageous to work with the do-it-yourselfers than to work against them.

The last thing Venter wants to do is kill off the curiosity. “We need to find a way to channel that great level of curiosity into places where people can get proper training, and at the same time exercise their curiosity in a healthy fashion,” he told NBC News. “Every university lab and serious research lab has that training. That’s where I’d start. I don’t think we need a new system for it.”

What is life? In Venter’s mind, public ignorance about biotech is a bigger problem than biotech’s risks. “It’s very hard to have a conversation when over 50 percent of people don’t know that tomatoes have DNA in them,” he said. “They don’t realize that every plant, animal, insect on the planet only exists because it has DNA software. The scaremongers and the worriers, that tells me that we need to greatly improve science education so we can at least start to have an intelligent conversation.”

Image: Life at the Speed of Light

Viking
J. Craig Venter delves into synthetic biology and its implications in “Life at the Speed of Light: From the Double Helix to the Dawn of Digital Life.”

Reading Venter’s latest volume provides a good antidote for biotech ignorance: The book was spawned by a talk he gave last year in Dublin, as a follow-up to Nobel-winning physicist Erwin Schrödinger’s famous lecture series titled “What Is Life?”

“Life at the Speed of Light” tells the story of biology from the 16th century to the current revolution in genetics, framed as a quest to understand how life is defined.

Venter has had a key role in that quest — as one of the leaders in the race to decode the human genome, as an adventurer seeking to catalog the ocean’s microbes, and as the head of a team that created the first synthetic genome in 2010.

Now his main focus is to “rewrite the software” for life, and enlist genetically engineered organisms to manufacture synthetic insulin, vaccines and other kinds of medicines; produce food and fuel for humanity; to clean up toxic waste sites and soak up atmospheric carbon dioxide.

DNA to beam up One of the tools that Venter and his colleagues are developing for the task is a “biological teleporter,” or digital-biological converter. Synthetic Genomics Inc., one of Venter’s ventures, has already built a prototype with backing from the Defense Advanced Research Projects Agency. The converter is designed to turn huge strings of digital code into synthetic molecules of DNA.

Future versions of such a device could read the code of an organism robotically at a remote site — say, beneath the surface of Mars — and beam the data back to a lab for reconstruction.

“We can rebuild the Martians in a P4 spacesuit lab — that is, a maximum-containment laboratory — instead of risking them splashing down in the ocean or crash-landing in the Amazon,” Venter writes. He suggests that the same technique could be used to reconstruct the life forms of aliens beaming their own information from distant planets. That’s assuming, of course, that E.T. is broadcasting the proper code on the proper channel.

And if life’s code could be sent at the speed of light from Mars or Gliese 581, couldn’t it be sent from Earth to the stars as well?

“In the past decade, since my own genome was sequenced, my software has been broadcast in the form of electromagnetic waves, carrying my genetic information far beyond Earth, as they ripple out into space,” Venter says in the book. “Borne upon those waves, my life now moves at the speed of light. Whether there is any life form out there capable of making sense of the instructions in my genome is yet another startling thought that spins out of that little question posed by Schrödinger half a century or more ago.”

 

Alan Boyle is NBCNews.com’s science editor. Connect with the Cosmic Log community by “liking” the NBC News Science Facebook page, following @b0yle on Twitter and adding +Alan Boyle to your Google+ circles. To keep up with NBCNews.com’s stories about science and space, sign up for the Tech & Science newsletter, delivered to your email in-box every weekday. You can also check out “The Case for Pluto,” my book about the controversial dwarf planet and the search for new worlds.

 

http://www.nbcnews.com/science/genomics-pioneer-craig-venter-warns-about-biohacker-boo-boos-8C11454274

Researchers advance toward engineering ‘wildly new genome’

Contact: David Cameron david_cameron@hms.harvard.edu 617-432-0441 Harvard Medical School

In two parallel projects, researchers have created new genomes inside the bacterium E. coli in ways that test the limits of genetic reprogramming and open new possibilities for increasing flexibility, productivity and safety in biotechnology.

In one project, researchers created a novel genome—the first-ever entirely genomically recoded organism—by replacing all 321 instances of a specific “genetic three-letter word,” called a codon, throughout the organism’s entire genome with a word of supposedly identical meaning. The researchers then reintroduced a reprogramed version of the original word (with a new meaning, a new amino acid) into the bacteria, expanding the bacterium’s vocabulary and allowing it to produce proteins that do not normally occur in nature.

In the second project, the researchers removed every occurrence of 13 different codons across 42 separate E. coli genes, using a different organism for each gene, and replaced them with other codons of the same function. When they were done, 24 percent of the DNA across the 42 targeted genes had been changed, yet the proteins the genes produced remained identical to those produced by the original genes.

“The first project is saying that we can take one codon, completely remove it from the genome, then successfully reassign its function,” said Marc Lajoie, a Harvard Medical School graduate student in the lab of George Church.  “For the second project we asked, ‘OK, we’ve changed this one codon, how many others can we change?'”

Of the 13 codons chosen for the project, all could be changed.

“That leaves open the possibility that we could potentially replace any or all of those 13 codons throughout the entire genome,” Lajoie said.

The results of these two projects appear today in Science. The work was led by Church, Robert Winthrop Professor of Genetics at Harvard Medical School and founding core faculty member at the Wyss Institute for Biologically Inspired Engineering. Farren Isaacs, assistant professor of molecular, cellular, and developmental biology at Yale School of Medicine, is co-senior author on the first study.

Toward safer, more productive, more versatile biotech

Recoded genomes can confer protection against viruses—which limit productivity in the biotech industry—and help prevent the spread of potentially dangerous genetically engineered traits to wild organisms.

“In science we talk a lot about the ‘what’ and the ‘how’ of things, but in this case, the ‘why’ is very important,” Church said, explaining how this project is part of an ongoing effort to improve the safety, productivity and flexibility of biotechnology.

“These results might also open a whole new chemical toolbox for biotech production,” said Isaacs. “For example, adding durable polymers to a therapeutic molecule could allow it to function longer in the human bloodstream.”

But to have such an impact, the researchers said, large swaths of the genome need to be changed all at once.

“If we make a few changes that make the microbe a little more resistant to a virus, the virus is going to compensate. It becomes a back and forth battle,” Church said. “But if we take the microbe offline and make a whole bunch of changes, when we bring it back and show it to the virus, the virus is going to say ‘I give up.’ No amount of diversity in any reasonable natural virus population is going to be enough to compensate for this wildly new genome.”

In the first study, with just a single codon removed, the genomically recoded organism showed increased resistance to viral infection. The same potential “wildly new genome” would make it impossible for engineered genes to escape into wild populations, Church said, because they would be incompatible with natural genomes. This could be of considerable benefit with strains engineered for drug or pesticide resistance, for example. What’s more, incorporating rare, non-standard amino acids could ensure strains only survive in a laboratory environment.

Engineering and evolution

Since a single genetic flaw can spell death for an organism, the challenge of managing a series of hundreds of specific changes was daunting, the researchers said. In both projects, the researchers paid particular attention to developing a methodical approach to planning and implementing changes and troubleshooting the results.

“We wanted to develop the ability to efficiently build the desired genome and to very quickly identify any problems—from design flaws or from undesired mutations — and develop workarounds,” Lajoie said.

The team relied on number oftechnologies developed in the Church lab and the Wyss Institute and with partners in academia and industry, including next-generation sequencing tools, DNA synthesis on a chip, and MAGE and CAGE genome editing tools. But one of the most important tools they used was the power of natural selection, the researchers added.

“When an engineering team designs a new cellphone, it’s a huge investment of time and money. They really want that cell phone to work,” Church said. “With E. coli we can make a few billion prototypes with many different genomes, and let the best strain win. That’s the awesome power of evolution.”

###

Funding was from Department of Energy [DE-FG02-02ER63445], NSF [SA5283-11210], NIH [NIDDK-K01DK089006], DARPA [N66001-12-C-4040, N66001-12-C-4020, N66001-12-C-4211], Arnold and Mabel Beckman Foundation, Department of Defense NDSEG Fellowship, NIH-MSTP-TG-T32GM07205, NSF graduate fellowship, NIH Director’s EarlyIndependence Award [Grant 1DP5OD009172-01], U.S. Office of Naval Research [N000141010144], Agilent Technologies, Wyss Institute, and Department of Defense NDSEG Fellowship, and Air Force Contract #FA8721-05-C-0002.

Written by JAKE MILLER

Harvard Medical School has more than 7,500 full-time faculty working in 11 academic departments located at the School’s Boston campus or in one of 47 hospital-based clinical departments at 16 Harvard-affiliated teaching hospitals and research institutes. Those affiliates include Beth Israel Deaconess Medical Center, Brigham and Women’s Hospital, Cambridge Health Alliance, Boston Children’s Hospital, Dana-Farber Cancer Institute, Harvard Pilgrim Health Care, Hebrew SeniorLife, Joslin Diabetes Center, Judge Baker Children’s Center, Massachusetts Eye and Ear Infirmary, Massachusetts General Hospital, McLean Hospital, Mount Auburn Hospital, Schepens Eye Research Institute, Spaulding Rehabilitation Hospital and VA Boston Healthcare System.

The Wyss Institute for Biologically Inspired Engineering at Harvard University uses Nature’s design principles to develop bioinspired materials and devices that will transform medicine and create a more sustainable world. Working as an alliance among Harvard’s Schools of Medicine, Engineering, and Arts & Sciences, and in partnership with Beth Israel Deaconess Medical Center, Brigham and Women’s Hospital, Boston Children’s Hospital, Dana Farber Cancer Institute, Massachusetts General Hospital, the University of Massachusetts Medical School, Spaulding Rehabilitation Hospital, Boston University, Tufts University, andCharité – Universitätsmedizin Berlin, the Institute crosses disciplinary andinstitutional barriers to engage in high-risk research that leads to transformative technological breakthroughs. By emulating Nature’s principles, Wyss researchers are developing innovative new engineering solutions for healthcare, energy, architecture, robotics, and manufacturing. These technologies are translated into commercial products and therapies through collaborations with clinical investigators, corporate alliances, and new start-ups. The Wyss Institute recently won the prestigious World TechnologyNetwork award for innovation in biotechnology.

Novel Strain of Clostridium botulinum That Produces Type B and Type H Botulinum Toxins

 

Jason R. Barash and

Stephen S. Arnon

+ Author Affiliations

Infant Botulism Treatment and Prevention Program, California Department of Public Health, Richmond, California

Correspondence: Stephen S. Arnon, MD, Infant Botulism Treatment and Prevention Program, California Department of Public Health, 850 Marina Bay Pkwy, Rm E-361, Richmond, CA 94804 (stephen.arnon@cdph.ca.gov).

Abstract

Background. Clostridium botulinum strain IBCA10-7060, isolated from a patient with infant botulism, produced botulinum neurotoxin type B (BoNT/B) and another BoNT that, by use of the standard mouse bioassay, could not be neutralized by any of the Centers for Disease Control and Prevention–provided monovalent polyclonal botulinum antitoxins raised against BoNT types A–G.

Methods and Results. The combining of antitoxins to neutralize the toxicity of known bivalent C. botulinum strains Ab, Ba, Af, and Bf also failed to neutralize the second BoNT. Analysis of culture filtrate by double immunodiffusion yielded a single line of immunoprecipitate with anti-A, anti-B, and anti-F botulinum antitoxins but not with anti-E antitoxin. A heptavalent F(ab’)2 botulinum antitoxin A–G obtained from the US Army also did not neutralize the second BoNT. An antitoxin raised against IBCA10-7060 toxoid protected mice against BoNT/B (Okra) and against the second BoNT but did not protect mice against BoNT/A (Hall) or BoNT/F (Langeland).

Conclusions. The second BoNT thus fulfilled classic criteria for being designated BoNT/H. IBCA10-7060 is the first C. botulinum type Bh strain to be identified. BoNT/H is the first new botulinum toxin type to be recognized in >40 years, and its recognition could not have been accomplished without the availability of the mouse bioassay.

 

http://jid.oxfordjournals.org/content/early/2013/10/07/infdis.jit449.short

Vaccination campaign doubles HBV mutations

Contact: Garth Hogan ghogan@asmusa.org 202-942-9389 American Society for Microbiology

WASHINGTON, DC – October 7, 2013 – A universal infant vaccination campaign in China has led the Hepatitis B virus (HBV) to more than double its rate of “breakout” mutations. These mutations may enable the virus to elude the vaccine, necessitating new vaccination strategies. Researchers at the Chinese Centers for Disease Control and Prevention and University of North Carolina, Chapel Hill, report their findings in an article published ahead of print in the Journal of Virology.

Until a universal vaccination program for infants was implemented in 1992, nearly ten percent of Chinese—children included—were infected with HBV. The vaccination campaign has protected an estimated 80 million children, dramatically reducing the percentage of children under 5 who are infected, from nearly 10 percent in 1992 to less than one percent in 2005. But these gains are in danger of being eroded as the virus develops surface mutations.

Taking advantage of 1992 and 2005 survey, investigators found that the prevalence of HBV escape mutants in children rose from 6.5 percent in 1992, before the start of the universal vaccination program, to nearly 15 percent in 2005. Among the control group of adults unaffected by the universal vaccination campaign, the rate of break-out mutants was virtually unchanged.

Hepatitis B is an infectious illness of the liver which can cause vomiting, inflammation, jaundice, and, rarely, death. About a third of the world’s population has been infected at some point in their lives. Transmission of hepatitis B virus results from exposure to infectious blood or bodily fluids containing blood. The infection is preventable by vaccination, which has been routinely used since the 1980s.

Researcher Tao Bian of Chapel Hill says that the vaccine remains quite effective, but that because escape mutants are likely to increase, public health officials need to track the rise of escape mutants, in order to know when it becomes time to consider new vaccination strategies. Measures that might be taken include boosting doses, adjusting the timing of vaccinations, or improving the vaccine. A next generation HBV vaccine has been invented, containing a second antigen in addition to the virus’ surface antigen. That means that both antigens would have to develop breakout mutations in order to elude the vaccine.

###

 

A copy of the manuscript can be found online at http://bit.ly/asmtip0913e.  Formal publication is scheduled for the November 2013 issue of the Journal of Virology.

The Journal of Virology is a publication of the American Society for Microbiology (ASM). The ASM is the largest single life science society, composed of over 39,000 scientists and health professionals. ASM’s mission is to advance the microbiological sciences as a vehicle for understanding life processes and to apply and communicate this knowledge for the improvement of health and environmental and economic well-being worldwide.

First estimate of total viruses in mammals ( Minimum of 320,000 viruses )

Contact: Timothy S. Paul tp2111@columbia.edu 212-305-2676 Columbia University’s Mailman School of Public Health

First estimate of total viruses in mammals

Minimum of 320,000 viruses; identifying them could help mitigate disease outbreaks; total cost less than a single pandemic

Scientists estimate that there is a minimum of 320,000 viruses in mammals awaiting discovery. Collecting evidence of these viruses, or even a majority of them, they say, could provide information critical to early detection and mitigation of disease outbreaks in humans. This undertaking would cost approximately $6.3 billion, or $1.4 billion if limited to 85% of total viral diversity — a fraction of the economic impact of a major pandemic like SARS.

Close to 70% of emerging viral diseases such as HIV/AIDS, West Nile, Ebola, SARS, and influenza, are zoonoses — infections of animals that cross into humans. Yet until now, there has been no good estimate of the actual number of viruses that exist in any wildlife species.

“Historically, our whole approach to discovery has been altogether too random,” says lead author Simon Anthony, D.Phil, a scientist at the Center for Infection and Immunity (CII) at Columbia University’s Mailman School of Public Health. “What we currently know about viruses is very much biased towards those that have already spilled over into humans or animals and emerged as diseases. But the pool of all viruses in wildlife, including many potential threats to humans, is actually much deeper. A more systematic, multidisciplinary, and One Health framework is needed if we are to understand what drives and controls viral diversity and following that, what causes viruses to emerge as disease-causing pathogens.”

“For decades, we’ve faced the threat of future pandemics without knowing how many viruses are lurking in the environment, in wildlife, waiting to emerge. Finally we have a breakthrough — there aren’t millions of unknown virus, just a few hundred thousand, and given the technology we have it’s possible that in my lifetime, we’ll know the identity of every unknown virus on the planet,” adds Peter Daszak, PhD, corresponding author and president of EcoHealth Alliance.

Secrets of the Flying Fox

To address the challenges of describing and estimating virodiversity, a team of investigators from CII and EcoHealth Alliance began in jungles of Bangladesh — home to the flying fox.  These bats are the largest flying mammal with a wingspan of up to 6 feet; they are also the source of several outbreaks of Nipah virus. The team collected 1,897 biological samples from the animals, which were captured and released. Back in the lab, they used polymerase chain reaction to identify 55 viruses in nine viral families. Of these, only five were previously known, including two human bocaviruses, an avian adenovirus, a human/bovine betacoronavirus, and an avian gammacoronavirus. Another 50 were newly discovered, including 10 in the same family as Nipah. Next the researchers adapted a statistical technique from the field of ecology to estimate that there were another three rare viruses unaccounted for in the samples, upping the estimate of viruses in the flying fox to 58. Finally, this number was extrapolated to all 5,486 known mammals, yielding a total of at least 320,000 viruses.

A Relative Bargain

The researchers then repeated the exercise for cost, extrapolating from an estimated $1.2 million for surveillance, sampling, and discovery of all 58 flying fox viruses to come up with a total of $6.3 billion for all mammals. Given the disproportionate cost of discovering rare viruses, they showed that limiting discovery to 85% of estimated viral diversity would bring the cost down to $1.4 billion.

“By contrast, the economic impact of the SARS pandemic is calculated to be $16 billion,” says Dr. Anthony. “We’re not saying that this undertaking would prevent another outbreak like SARS. Nonetheless, what we learn from exploring global viral diversity could mitigate outbreaks by facilitating better surveillance and rapid diagnostic testing.”

“If we know what’s out there, we’ll be a lot better prepared when a virus jumps over into a human population,” Dr. Anthony continues, adding that prevention is crucial when it comes to viral infections since antivirals are notoriously difficult to develop.

Plumbing the Depths of the Zoonotic Pool

A continued systematic effort to discover mammal viruses would provide a more accurate estimate on total number of viruses in what co-author Stephen Morse, PhD, co-director of the PREDICT Project and professor of Epidemiology at the Mailman School, calls the “zoonotic pool” of potential viral pathogens that threaten humans.

The researchers say the initial estimate of 320,000 is just a starting point and will likely be considerably higher after accounting for additional viral families and employing high throughput sequencing methods developed at CII.  They also point to several unknowns, including whether or not the samples from flying foxes in Bangladesh are representative of all flying foxes, which range across Southern Asia; whether or not all mammal species harbor a similar number of viruses; and the extent to which viruses are shared from species to species (as seen with the human, bovine, and avian viruses in the flying fox). Furthermore, the cost of collecting samples could vary depending on habitat (the flying fox expedition in Bangladesh was relatively low compared with similar undertaking for an animal living in more remote areas).

To help fill in some of these blanks, the team is repeating the process in two follow-up studies — one in a species of primates in Bangladesh in order to see if their viral diversity is comparable to the flying fox’s, and another in Mexico, where analysis of samples from six species of bats that share the same habitat will be undertaken to determine the extent to which they share viruses. With additional resources, they hope to expand the investigation to other species and viral families.

“To quote Benjamin Franklin, an ounce of prevention is worth a pound of cure,” says senior author W. Ian Lipkin, MD, director of CII. “Our goal is to provide the viral intelligence needed for the global public health community to anticipate and respond to the continuous challenge of emerging infectious diseases.”

In fact, this type of large-scale zoonotic virus discovery and characterization is now being done in an economically efficient way through the PREDICT Project, funded by the United States Agency for International Development (USAID). The work described in the study has been integral to the Project’s success.

“PREDICT has already discovered more than 240 novel viruses throughout the world in areas where people and animals live in close contact and depend on the same natural resources,” says study co-author Jonna Mazet, PhD, director of the UC Davis One Health Institute and co-director of PREDICT. “That includes new coronaviruses, like the ones that cause SARS and the new Middle East Respiratory Syndrome.”

###

 

The current study follows the One Health approach, which considers the interdependence of the health of people, animals, and the environment.  It is a multidisciplinary collaboration between 21 molecular virologists, ecologists, veterinarians, and mathematicians from institutions, including the Center for Infection and Immunity at Columbia’s Mailman School; EcoHealth Alliance, National Autonomous University of Mexico, University of California, Davis; International Centre for Diarrhoeal Disease Research, Dhaka (Bangladesh); Princeton University; National Institutes of Health; and Chittagong Veterinary and Animal Sciences University (Bangladesh).

The study, titled “A strategy to estimate unknown viral diversity in mammals,” appears in the journal mBio.

Compared to Syrian biological weapons, sarin is nothing – official

инфекция анализы врач пробирка эпидемия свиной грипп H1N1 птичий грипп

Photo: RIA Novosti

The issue of chemical and biological weapons in Syria is creating concerns in both neighbouring and distant countries. The mere presence of such weapons in the hands of the Syrian rebels is seen as a threat in itself, as they have not hesitated to use them against civilians twice in the recent year.

Syria’s bioweapons program, which US officials believe has been largely dormant since the 1980s, is likely to possess the key ingredients for a biological and chemical weapons, including a collection of lethal bacteria and viruses as well as the modern equipment needed to covert them into deadly powders and aerosols, according to US and Middle Eastern officials and weapons experts.

This latent capability has begun to worry some of Syria’s neighbors, especially after allegations that the regime of President Bashar al-Assad used internationally banned chemical weapons against civilians in an Aug. 21 Ghouta attack.

Top intelligence officials in two Middle East countries said they have examined the potential for bioweapons use by Syria, perhaps as retaliation for Western military strikes on Damascus. Although dwarfed by the country’s larger and better-known chemical weapons program, Syria’s bioweapons capability could offer the Assad regime a way to retaliate because the weapons are designed to spread easily and leave few clues about their origins, the officials said.

“We are worried about sarin, but Syria also has biological weapons, and compared to those, sarin is nothing,” a senior Middle Eastern official told Washtington Post. “We know it, and others in the region know it. The Americans certainly know it.”

US officials acknowledge the possibility of a latent bioweapons capability but are divided about whether Syria is capable of a sophisticated attack.

However, if Syrian rebels cannot carry out such an attack, al-Qaeda affiliated in Iraq most certainly can.

Recent reports indicating al-Qaeda in Iraq is seeking to obtain bioweapons raises serious concern about those weapons reaching al-Qaeda affiliates JAN and ISIL, or the Syrian bioweapons falling into their hands.

The Iraqi government announced in June it had arrested members of an al-Qaeda cell who confessed they intended to carry out bioweapon attacks in Iraq and neighbouring countries.

Further investigations revealed that plans were put in place for al-Qaeda affiliate JAN to get access to those weapons and “further aggravate the tragedy of the Syrian people,” according to Iraqi national security advisor Faleh al-Fayyadh.

Security forces shut down two factories, one in Baghdad and the other in an area near the capital, and confiscated biological compounds and the equipment used in their manufacture, the government said in a statement. Confiscated items included a remote-controlled toy plane that was to carry bioweapons to be dropped over a relatively distant target.

Voice of Russia, Central Asia Online, Washington Post

http://voiceofrussia.com/news/2013_09_05/Compared-to-Syrias-biological-weapons-sarin-is-nothing-official-8179/

 

Flu vaccine backfires in pigs / vaccinated against H1N2 influenza were more vulnerable to the rarer H1N1 strain

Antibodies against one strain increase risk of infection with another.

28 August 2013
Pigs vaccinated against H1N2 influenza were more vulnerable to the rarer H1N1 strain.

Andy Rouse/Photoshot

Preventing seasonal sniffles may be more complicated than researchers suspected. A vaccine that protects piglets from one common influenza virus also makes them more vulnerable to a rarer flu strain, researchers report today in Science Translational Medicine1.

The team gave piglets a vaccine against H1N2 influenza. The animals responded by making antibodies that blocked that virus — but aided infection with the swine flu H1N1, which caused a pandemic among humans in 2009. In the study, H1N1 infected more cells and caused more severe pneumonia in vaccinated piglets than unvaccinated ones.

The root of the different immune responses lies with the mushroom-shaped haemagglutinin protein found on the outside of influenza-virus particles, which helps them to attach onto cells in the airways. The protein occurs in all types of flu, but the make-up of its cap and stem vary between strains.

In the study, a vaccine for H1N2 spurred pigs to produce antibodies that bound the cap and the stem of that virus’s haemagglutinin. But some of those antibodies also targeted the stem of H1N1’s haemagglutinin protein, helping that virus fuse to cell membranes. That made H1N1 more efficient at infecting pigs and causing disease.

Stem vaccines

The finding may give some vaccine developers pause. Much of the work to develop a universal flu vaccine has targeted the stems of haemagglutinin proteins, because they are relatively consistent across many types of influenza viruses.

The new study suggests that such vaccines could also produce antibodies that enhance the ability of some viruses to infect new hosts, says James Crowe, an immunologist at Vanderbilt University in Nashville, Tennessee. But that does not mean that researchers should stop developing novel flu vaccines, including those that target haemagglutinin stems, he adds. “We should be very careful.”

Gary Nabel, a flu-vaccine researcher and chief scientific officer at the biotechnology firm Sanofi in Cambridge, Massachusetts, agrees. “It raises a warning flag, but at the same time it provides a tool to manage that risk,” he says of the new study’s results and methods.

Still, researchers have not yet tested whether human influenza vaccines can produce the same effect. And differences between pigs and humans make it difficult to interpret how relevant the findings are to the development of human vaccines, says Sarah Gilbert, a vaccine researcher at the University of Oxford, UK.

Lead author Hana Golding, a microbiologist at the US Food and Drug Administration in Bethesda, Maryland, agrees — and stresses that seasonal vaccines are still safe and effective. “This has no relevance to the regular vaccinations,” she says. “We think that people should definitely take them.”

Journal name:
Nature
DOI:
doi:10.1038/nature.2013.13621

References

  1. Khurana, S. et al. Sci. Transl. Med. 5, 200ra114 (2013).

 

http://www.nature.com/news/flu-vaccine-backfires-in-pigs-1.13621

The Hidden Threat That Could Prevent Polio’s Global Eradication – Vaccinated Children that Become “chronic excreters”

 

Polio could soon be wiped out—but only if scientists can track down the last carriers

By Helen Branswell

 


Image: GETTY IMAGES

Global eradication of polio has been the ultimate game of Whack-a-Mole for the past decade; when it seems the virus has been beaten into submission in a final refuge, up it pops in a new region. Now, as vanquishing polio worldwide appears again within reach, another insidious threat may be in store from infection sources hidden in plain view.

Polio’s latest redoubts are “chronic excreters,” people with compromised immune systems who, having swallowed weakened polioviruses in an oral vaccine as children, generate and shed live viruses from their intestines and upper respiratory tracts for years. Healthy children react to the vaccine by developing antibodies that shut down viral replication, thus gaining immunity to infection. But chronic excreters cannot quite complete that process and instead churn out a steady supply of viruses. The oral vaccine’s weakened viruses can mutate and regain wild polio’s hallmark ability to paralyze the people it infects. After coming into wider awareness in the mid-1990s, the condition shocked researchers.

Philip Minor, deputy director of the U.K.’s National Institute for Biological Standards and Control, describes the biomedical nightmare: Wild polioviruses stop circulating. Countries cut back on vaccination efforts. A chronic excreter kisses an unvaccinated baby, and the baby goes to day care. “And zappo,” he adds, “it’s all over the place, with babies drooling all over each other. So you could see a scenario where polio would come back from a developed country.” It could happen in the developing world as well. Although it was once thought that immunocompromised individuals could not survive for long in lower-income countries, circumstances are changing as those countries improve their health care systems. In 2009 an immunodeficient 11-year-old Indian boy was paralyzed by polio, five years after swallowing a dose of oral vaccine. It was only then that researchers recognized him as a chronic excreter.

Chronic excreters are generally only discovered when they develop polio after years of surreptitiously spreading the virus. Thankfully, such cases are rare. According to Roland W. Sutter, the World Health Organization scientist who heads research policy for the Global Polio Eradication Initiative, the initiative is pushing for the development of drugs that could turn off vaccine virus shedding. A few promising options are in the pipeline.

Drugs can only solve the problem if chronic excreters are identified, and that’s no easy task. For years scientists in Finland, Estonia and Israel monitored city sewers, watching for signs of shedders’ presence. In many samples, they have found the telltale viruses from chronic excreters, but they have failed to locate any of the individuals. These stealthy shedders may not be classic immunodeficient patients traceable through visits to immunologists. Instead they may be people who do not know they have an immunity problem at all and are under no specialized medical care. “We know that there’s really a Damocles sword hanging over them,” Sutter says. It hangs over the rest of us as well.

This article was originally published with the title Hidden and Dangerous.

 

http://www.scientificamerican.com/article.cfm?id=hidden-threat-that-could-prevent-polio-global-eradication

Scientists to make mutant forms of new bird flu to assess risk

Source: Reuters – Wed, 7 Aug 2013 05:00 PM

Author: Reuters

 

* Controversial research sparked previous security fears

* Flu experts say it is critical to prepare for threat

* New H7N9 bird flu strain has killed 43 people so far

* Outbreak currently controlled, may return in autumn

By Kate Kelland, Health and Science Correspondent

LONDON, Aug 7 (Reuters) – Scientists are to create mutant forms of the H7N9 bird flu virus that has emerged in China so they can gauge the risk of it becoming a lethal human pandemic.

The genetic modification work will to result in highly transmissible and deadly forms of H7N9 being made in several high security laboratories around the world, but it is vital to prepare for the threat, the scientists say.

The new bird flu virus, which was unknown in humans until February, has already infected at least 133 people in China and Taiwan, killing 43 of them, according to the latest World Health Organization (WHO) data.

Announcing plans to start the controversial experiments, leading virologists Ron Fouchier and Yoshihiro Kawaoka said H7N9’s pandemic risk would rise “exponentially” if it gained the ability to spread easily among people.

And the only way to find out how likely that is, and how many genetic changes would need to take place before it could happen, is to engineer those mutations in laboratory conditions  and test the virus’s potential using animal models, they said.

“It’s clear this H7N9 virus has some hallmarks of pandemic viruses, and it’s also clear it is still missing at least one or two of the hallmarks we’ve seen in the pandemic viruses of the last century,” Fouchier told Reuters in a telephone interview.

“So the most logical step forward is to put in those (missing) mutations first.”

Writing in the journals Nature and Science on behalf of 22 scientists who will carry out various aspects of the H7N9 work, Fouchier said because the risk of a pandemic caused by a bird flu virus exists in nature, it was critical for risk-mitigation plans to study the likely mutations that could make that happen.

This kind of science is known as “gain of function” (GOF) research. It aims to identify combinations of genetic mutations that allow an animal virus to jump to humans and spread easily.

By finding the mutations needed, researchers and health authorities can better assess how likely it is that a new virus could become dangerous and if so, how soon they should begin developing drugs, vaccines and other scientific defences.

Yet such work is highly controversial. It has fuelled an international row in the past two years after it was carried out on another threatening bird flu virus called H5N1.

BIOTERRORISM FEARS

When Fouchier, of the Erasmus Medical Centre in Rotterdam, The Netherlands, and Kawaoka, at the University of Wisconsin in the United States, announced in late 2011 they had found how to make H5N1 into a form that could spread between mammals, the U.S. National Science Advisory Board for Biosecurity (NSABB) was so alarmed that it took the unprecedented step of trying to censor publication of the studies.

The NSABB said it feared details of the work could fall into the wrong hands and be used for bioterrorism. A year-long moratorium on such research followed while the World Health Organisation, U.S. security advisers and international flu researchers sought ways to ensure the highest safety controls.

The laboratory Fouchier will be working in is known as a  BSL3 Enhanced lab (Bio-Safety Level 3), the highest level of biosecurity that can be achieved in academic research.

“Nature is the biggest threat to us, not what we do in the lab. What we do in the lab is under very intense biosecurity measures,” he said. “There are layers upon layers of layers of biosafety measures such that if one layer might break there are additional layers to prevent this virus ever coming out.”

Fouchier conceded that GOF research has been “under fire” recently. “One of the accusations against the flu community was that we were not transparent enough about what experiments were being done, and why and how they were being done,” he said. “We’re trying to pre-empt such accusations this time.”

The H7N9 bird flu outbreak currently appears under control with only 3 new human cases in May after 87 in April and 30 in March. Experts say this is largely thanks to the closure of many live poultry markets and because of warmer weather.

Yet as winter approaches in China, many experts believe H7N9 could re-emerge, meaning the threat of a pandemic looms if it mutates to become easily transmissible between people.

The first scientific analysis of probable human-to-human transmission of H7N9 raised concern about its pandemic potential and prompted scientists James Rudge and Richard Coker of the London School of Hygiene and Tropical Medicine to warn: “The threat posed by H7N9 has by no means passed.”

Fouchier and colleagues said they hope to unravel the molecular processes behind H7N9 by manipulating its genetic material to increase virulence or induce drug resistance.

Wendy Barclay, an Imperial College London flu expert, said it would be ludicrous to shy away from such studies. “This type of work is like fitting glasses for someone who can’t see well,” she said. “Without the glasses the vision is blurred and uncertain, with them you can focus on the world and deal with it a lot more easily.”   (Reporting by Kate Kelland; editing by David Evans)

http://www.trust.org/item/20130807165536-m5jun/?source=hpbreaking

 

Georgia conducts dangerous experiments with viruses: “experiments with viruses have led to the spread of such dangerous illnesses as pig flu and measles”

бактерия вирус германия вирус

Photo: EPA

The people of Georgia are in danger. This sensational statement was made by the Georgian President’s former American advisor, journalist Jeffrey Silverman. According to him, a laboratory on the outskirts of Tbilisi is developing health hazardous viruses that are being tested on local residents.

 The laboratory is named after American senator Richard Lugar. This is not a mere coincidence. The laboratory was opened with the assistance of the American government. According to official information, specialists at the laboratory study the genetics of bacteria and viruses. However, former advisor to the President Jeffrey Silverman believes that the laboratory is engaged in developing viruses rather than studying them.

Download audio file

 Reportedly, in 2001-2003, Silverman helped Mikhail Saakashvili to carry out his presidential campaign. But later their paths diverged. The latest statement by Silverman that residents of Georgia have become a target of dangerous experiments is one of the most discussed topics in Georgia now. According to Silverman, experiments with viruses have led to the spread of such dangerous illnesses as pig flu and measles. In fact, deputy director of the National Agency for Diseases Control Paata Imnadze says that a rise in infection rate has nothing to do with the laboratory.

 “At present, elder people are getting sick because their immunity is low. In 2008, we launched a large-scale campaign to vaccinate one million. But we vaccinated only 500,000. At present, we see its consequences,” Paata Imnadze said.

 The Georgian government described the statement as absurd. A deputy of the Georgian parliament Irina Imerlishvili says the laboratory is a scientific research institute, but not the Pentagon’s biological weapon department.

 “The laboratory was opened during President Saakashvili’s rule. He himself attended the ceremony. It’s well-known that Saakashvili does not love his people and loves to conduct experiments on them, of course. However, I believe that it has nothing to do with this case,” Irina Imerlishvili said.

 The President’s former advisor’s scandalous statement has not confirmed yet. Outsiders are banned from entering the laboratory. The workers are allowed to enter the building after several checks. However, Silverman is ready to go further. He promised to tell Georgians the whole truth about their leader shortly.

 Boris Murashkin

http://english.ruvr.ru/2013_05_06/Georgia-conducts-dangerous-experiments-with-viruses/

 

Scientists create hybrid flu that can go airborne : Mixed Genes from H5N1 & H1N1

H5N1 virus with genes from H1N1 can spread through the air between mammals.

02 May 2013

Researchers have crossed two strains of avian flu virus to create one that can be transmitted through the air — and possibly settle on the cilia of lung cells as in this conceptual image.

KARSTEN SCHNEIDER/SCIENCE PHOTO LIBRARY

As the world is transfixed by a new H7N9 bird flu virus spreading through China, a study reminds us that a different avian influenza — H5N1 — still poses a pandemic threat.

A team of scientists in China has created hybrid viruses by mixing genes from H5N1 and the H1N1 strain behind the 2009 swine flu pandemic, and showed that some of the hybrids can spread through the air between guinea pigs. The results are published in Science1.

Flu hybrids can arise naturally when two viral strains infect the same cell and exchange genes. This process, known as reassortment, produced the strains responsible for at least three past flu pandemics, including the one in 2009.

There is no evidence that H5N1 and H1N1 have reassorted naturally yet, but they have many opportunities to do so. The viruses overlap both in their geographical range and in the species they infect, and although H5N1 tends mostly to swap genes in its own lineage, the pandemic H1N1 strain seems to be particularly prone to reassortment.

“If these mammalian-transmissible H5N1 viruses are generated in nature, a pandemic will be highly likely,” says Hualan Chen, a virologist at the Harbin Veterinary Research Institute of the Chinese Academy of Sciences, who led the study.

“It’s remarkable work and clearly shows how the continued circulation of H5N1 strains in Asia and Egypt continues to pose a very real threat for human and animal health,” says Jeremy Farrar, director of the Oxford University Clinical Research Unit in Ho Chi Minh City, Vietnam.

Flu fears

Chen’s results are likely to reignite the controversy that plagued the flu community last year, when two groups found that H5N1 could go airborne if it carried certain mutations in a gene that produced a protein called haemagglutinin (HA)2, 3. Following heated debate over biosecurity issues raised by the work, the flu community instigated a voluntary year-long moratorium on research that would produce further transmissible strains. Chen’s experiments were all finished before the hiatus came into effect, but more work of this nature can be expected now that the moratorium has been lifted.

“I do believe such research is critical to our understanding of influenza,” says Farrar. “But such work, anywhere in the world, needs to be tightly regulated and conducted in the most secure facilities, which are registered and certified to a common international standard.”

Virologists have created H5N1 reassortants before. One study found that H5N1 did not produce transmissible hybrids when it reassorts with a flu strain called H3N24. But in 2011, Stacey Schultz-Cherry, a virologist at St. Jude Children’s Research Hospital in Memphis, Tennessee, showed that pandemic H1N1 becomes more virulent if it carries the HA gene from H5N15.

Chen’s team mixed and matched seven gene segments from H5N1 and H1N1 in every possible combination, to create 127 reassortant viruses, all with H5N1’s HA gene. Some of these hybrids could spread through the air between guinea pigs in adjacent cages, as long as they carried either or both of two genes from H1N1 called PA and NS. Two further genes from H1N1, NA and M, promoted airborne transmission to a lesser extent, and another, the NP gene, did so in combination with PA.

“It’s a very extensive paper,” says Schultz-Cherry. “It really shows that it’s more than just the HA. The other proteins are just as important and can drive transmission.” Chen says that health organisations should monitor wild viruses for the gene combinations that her team identified in the latest study. “If those kinds of reassortants are found, we’d need to pay high attention.”

Knowledge gap

It is unclear how the results apply to humans. Guinea pigs have bird-like receptor proteins in their upper airways in addition to mammalian ones, so reassortant viruses might bind in them more easily than they would in humans.

And scientists do not know whether the hybrid viruses are as deadly as the parent H5N1. The hybrids did not kill any of the guinea pigs they spread to, but Chen says that these rodents are not good models for pathogenicity in humans.

There is also a chance that worldwide exposure that already occurred to the pandemic H1N1 strain might actually mitigate the risk of a future pandemic by providing people with some immunity against reassortants with H5N1. In an earlier study, Chen and her colleagues showed that a vaccine made from pandemic H1N1 provided some protection against H5N1 infections in mice6.

“If you take [antibodies] from people who have been vaccinated or naturally infected, will they cross-react with these viruses?” asks Schultz-Cherry. “That’s an important study that would need to be done.”

Ironically, Chen’s team is now too busy reacting to the emerging threat of a different bird flu — H7N9. Research on H5N1 will have to wait.

Journal name:
Nature
DOI:
doi:10.1038/nature.2013.12925
http://www.nature.com/news/scientists-create-hybrid-flu-that-can-go-airborne-1.12925

‘Appalling irresponsibility’: Senior scientists attack Chinese researchers for creating new strains of influenza virus in veterinary laboratory

Experts warn of danger that the new viral strains created by mixing bird-flu virus with human influenza could escape from the laboratory to cause a global pandemic killing millions of people.

Steve Connor

Thursday, 2 May 2013

Senior scientists have criticised the “appalling irresponsibility” of researchers in China who have deliberately created new strains of influenza virus in a veterinary laboratory.

They warned there is a danger that the new viral strains created by mixing bird-flu virus with human influenza could escape from the laboratory to cause a global pandemic killing millions of people.

Lord May of Oxford, a former government chief scientist and past president of the Royal Society, denounced the study published today in the journal Science as doing nothing to further the understanding and prevention of flu pandemics.

“They claim they are doing this to help develop vaccines and such like. In fact the real reason is that they are driven by blind ambition with no common sense whatsoever,” Lord May told The Independent.

“The record of containment in labs like this is not reassuring. They are taking it upon themselves to create human-to-human transmission of very dangerous viruses. It’s appallingly irresponsible,” he said.

The controversial study into viral mixing was carried out by a team led by Professor Hualan Chen, director of China’s National Avian Influenza Reference Laboratory at Harbin Veterinary Research Institute.

Professor Chen and her colleagues deliberately mixed the H5N1 bird-flu virus, which is highly lethal but not easily transmitted between people, with a 2009 strain of H1N1 flu virus, which is very infectious to humans.

When flu viruses come together by infecting the same cell they can swap genetic material and produce “hybrids” through the re-assortment of genes. The researchers were trying to emulate what happens in nature when animals such as pigs are co-infected with two different strains of virus, Professor Chen said.

“The studies demonstrated that H5N1 viruses have the potential to acquire mammalian transmissibility by re-assortment with the human influenza viruses,” Professor Chen said in an email.

“This tells us that high attention should be paid to monitor the emergence of such mammalian-transmissible virus in nature to prevent a possible pandemic caused by H5N1 virus,” she said.

“It is difficult to say how easy this will happen, but since the H5N1 and 2009/H1N1 viruses are widely existing in nature, they may have a chance to re-assort,” she added.

The study, which was carried out in a laboratory with the second highest security level to prevent accidental escape, resulted in 127 different viral hybrids between H5N1 and H1N1, five of which were able to pass by airborne transmission between laboratory guinea pigs.

Professor Simon Wain-Hobson, an eminent virologist at the Pasteur Institute in Paris, said it is very likely that some or all of these hybrids could pass easily between humans and possess some or all of the highly lethal characteristics of H5N1 bird-flu.

“Nobody can extrapolate to humans except to conclude that the five viruses would probably transmit reasonable well between humans,” Professor Wain-Hobson said.

“We don’t know the pathogenicity [lethality] in man and hopefully we will never know. But if the case fatality rate was between 0.1 and 20 per cent, and a pandemic affected 500 million people, you could estimate anything between 500,000 and 100 million deaths,” he said.

“It’s a fabulous piece of virology by the Chinese group and it’s very impressive, but they haven’t been thinking clearly about what they are doing. It’s very worrying,” Professor Wain-Hobson said.

“The virological basis of this work is not strong. It is of no use for vaccine development and the benefit in terms of surveillance for new flu viruses is oversold,” he added.

An increasing number of scientists outside the influenza field have expressed concern over attempts to deliberately increase the human transmissibility of the H5N1 bird-flu virus. This is done by mutating the virus so that it can pass by airborne droplets between laboratory ferrets, the standard “animal model” of human influenza.

Two previous studies, by Ron Fouchier of Erasmus Medical Centre in Rotterdam and Yoshihiro Kawaoka of the University of Wisconsin, Madison, caused uproar in 2011 when it emerged that they had created airborne versions of H5N1 that could be passed between ferrets.

The criticism led to researchers to impose a voluntary moratorium on their H5N1 research, banning transmission studies using ferrets. However they decided to lift the ban earlier this year, arguing that they have now consulted widely with health organisations and the public over safety concerns.

However, other scientists have criticised the decision to lift the moratorium.

Large HIV study stopped after safety review found more study participants who received the vaccine later became infected

HIV vaccine study halted by US government over unsuccessful shots

Associated Press in Washington

guardian.co.uk,  Thursday 25 April 2013 17.52 EDT

A pharmaceutical machine loaded with ARV medicine at the Themba Lethu HIV/Aids clinic, Johannesburg

A 2009 study in Thailand is the only HIV/Aids study ever to show a modest success. Photograph: Denis Farrell/AP

The US government halted a large HIV vaccine study on Thursday, saying the experimental shots were not successful in preventing infection.

Nor did the shots reduce the amount of the Aids virus in the blood when people who had been vaccinated later became infected, the National Institutes of Health said.

“It’s disappointing,” said Dr Anthony Fauci, head of NIH’s National Institute of Allergy and Infectious Diseases. But he said there was “important information” gained from the study that will help determine what to try next.

The study had enrolled 2,504 volunteers, mostly gay men, in 19 cities since 2009. Half received dummy shots, and half received a two-part experimental vaccine developed by the NIH. All were provided free condoms and given extensive counseling about the risks of HIV.

It’s a strategy known as “prime-boost”. A DNA-based vaccine made with genetically engineered HIV material is given to prime the immune system to attack the Aids virus. Then a different vaccine, encasing the same material inside a shell made of a disabled cold virus, acts as a booster shot to strengthen that response. Neither vaccine could cause HIV.

The idea was to train immune cells known as T cells to spot and attack the very earliest HIV-infected cells in someone’s body. The hope was that the vaccine could either prevent HIV infection, or help those infected anyway to fight it.

A safety review this week found that slightly more study participants who had received the vaccine later became infected with HIV. It’s not clear why. But the difference wasn’t statistically significant, meaning it may be due to chance. Overall, there were 41 HIV infections in the vaccinated group and 30 among placebo recipients. When researchers examined only participants diagnosed after being in the study for at least 28 weeks – long enough for the shots to have done their job – there were 27 HIV infections among the vaccinated and 21 among the placebo recipients.

The NIH said Thursday that it is stopping vaccinations in the study, known as HVTN 505, but that researchers will continue to study the volunteers’ health.

Josh Robbins, 30, of Nashville, Tennessee, was one of the participants who became infected with HIV. He said he was glad he had taken part because its close monitoring meant he was diagnosed and treated much sooner than most people.

“We’ve got to keep moving forward,” Robbins said. The study “certainly can lead us down a new direction to hopefully find something that might work.”

Multiple attempts at creating an Aids vaccine have failed over the years. A 2009 study in Thailand is the only one ever to show a modest success, using a somewhat different prime-boost approach. Newer research suggests another approach – to try creating powerful antibodies that could work a step earlier than the T-cell attack, before HIV gets inside the first cell.

Both approaches need continued research funding, said Mitchell Warren of the international Aids Vaccine Advocacy Coalition.  “Clearly an Aids vaccine remains critical,” he said.

http://www.guardian.co.uk/society/2013/apr/25/hiv-aids-vaccine-study-us-government

 

MMR scare doctor Andrew Wakefield breaks his silence: Measles outbreak in Wales proves I was right

As measles cases rise, experts condemn Wakefield’s outburst

Jeremy Laurance

Saturday, 13 April 2013

The discredited doctor who triggered the MMR scare 15 years ago has pinned the blame for the outbreak of measles in south Wales on the Government.

In an extraordinary intervention, Andrew Wakefield, who was struck off the medical register, said the “British Government is entirely culpable” for the outbreak and accused officials of “putting price before children’s health” – despite a widespread consensus that it was the panic over his flawed research that led to the surge in the disease.

The number of measles cases in the Swansea area rose to 693 on Thursday. It is now the largest outbreak in the country for over a decade, exceeding the 622 cases recorded in Merseyside in 2012.

Public Health Wales warned that the outbreak was unlikely to peak for “two to three” weeks because of the incubation period for measles. Children return to school after the Easter holiday on Monday and will begin mixing with a wider group of their peers, which could accelerate the spread of the disease.

Health officials urged parents to take their children to one of the drop-in vaccination clinics set up in the wake of the outbreak.

They say at least 6,000 people remain unprotected in south-west Wales and it is only a matter of time before a child develops serious complications as a result.

Dr Wakefield was the chief author of the now infamous and discredited 1998 Lancet paper that first linked the MMR vaccine with bowel disease and autism. In a statement posted on Thursday on  the US website Age of Autism, he blamed the rise in measles in the UK on the Government’s decision to withdraw import licences for single vaccines in September 1998, six months after the Lancet paper appeared.

He said the Government was more interested in protecting the MMR programme than protecting children and challenged “any serious defender of MMR vaccine safety” to a debate on live television.

He had recommended the use of single measles vaccine at the press conference to launch the Lancet paper and said that “remains my position”.

But when, in 1998, he asked the UK Health Protection Agency why the import licences for single vaccines had been revoked he says he was told that allowing parents the choice would “destroy our MMR programme”.

“The Government’s concern appeared to be to protect the MMR programme over and above the protection of children,” he claims.

He accused officials of having approved “dangerous” brands of MMR vaccine a decade earlier in 1988, when the vaccine was first launched in the UK, which later had to be withdrawn because they “caused meningitis”.

“These government officials put price before children’s health and have been seeking to cover up this shameful fact ever since.”

He cites cases in the courts in the US and Italy where families of children suffering autism have won damages worth hundreds of thousands of dollars after judges accepted the children had suffered “vaccine-induced brain damage”.

Adam Finn, professor of paediatrics at the University of Bristol and an expert on childhood vaccines described Dr Wakefield’s claims as “balderdash”.

“His proposal for single vaccines was not based on any observations in his published paper. It came straight out of his head. There has never been any evidence it would have made any difference.

“There were, however, real concerns that sticking more needles in children was unkind, fewer children would show up for each round and they would face delays in getting protected. Single measles vaccine is only used in poorer countries that cannot afford MMR. No country in the world has switched from MMR to single vaccines.”

Professor Finn said there had been a problem in the early years of MMR with one strain of the mumps virus used in the vaccine causing a transient form of aseptic meningitis. The make-up of the vaccine was changed, but the facts were well known and had not been covered up.

In relation to the court cases, he said it was important not to confuse principles of justice with the principles of science.

“Judges look at the case in front of them and make a judgement as best they can. They don’t do it in a systematic way as scientists do.”

In 2010, The Lancet retracted Dr Wakefield’s research paper and he was struck off the medical register by the General Medical Council.

The GMC verdict found that he had acted “dishonestly and irresponsibly”, showed “callous disregard for children’s suffering” and betrayed patients’ trust.

But the affair sparked a media storm which saw vaccination rates plummet, hundreds of thousands of children left unprotected, and measles cases soar.

Dr Wakefield moved to Texas, US, in 2001 where he is director of Medical Interventions for Autism and in January was promoting a reality TV series on autism.

 

http://www.independent.co.uk/life-style/health-and-families/health-news/mmr-scare-doctor-andrew-wakefield-breaks-his-silence-measles-outbreak-in-wales-proves-i-was-right-8570594.html#

Scientists described small genetic changes that enable the H5N1 bird flu virus to replicate more easily in the noses of mammals

 

Bird flu mutation study offers vaccine clue

by  Sam Wong   08 April 2013                   

main image

 

shadow Scientists have described small genetic changes that enable the H5N1 bird flu virus to replicate more easily in the noses of mammals.

So far there have only been isolated cases of bird flu in humans, and no widespread transmission as the H5N1 virus can’t replicate efficiently in the nose. The new study, using weakened viruses in the lab, supports the conclusions of controversial research published in 2012 which demonstrated that just a few genetic mutations could enable bird flu to spread between ferrets, which are used to model flu infection in humans.

Researchers say the new findings could help to develop more effective vaccines against new strains of bird flu that can spread between humans.

“Knowing why bird flu struggles to replicate in the nose and understanding the genetic mutations that would enable it to happen are vital for monitoring viruses circulating in birds and preparing for an outbreak in humans,” said Professor Wendy Barclay, from the Department of Medicine at Imperial College London, who led the study.

“The studies published last year pointed to a mechanism that restricts replication of H5N1 viruses in the nose. We’ve engineered a different mutation with the same effect into one of the virus proteins and achieved a similar outcome. This suggests that there is a common mechanism by which bird flu could evolve to spread between humans, but that a number of different specific mutations might mediate that.”

Bird flu only rarely infects humans because the human nose has different receptors to those of birds and is also more acidic. The Imperial team studied mutations in the gene for haemagglutinin, a protein on the surface of the virus that enables it to get into host cells. They carried out their experiments in a laboratory strain of flu with the same proteins on its surface as bird flu, but engineered so that it cannot cause serious illness.

The more we understand about the kinds of mutations that will enable them to transmit between humans, the better we can prepare for a possible pandemic.– Professor Wendy Barclay

Department of Medicine

The research found that mutations in the H5 haemagglutinin enabled the protein to tolerate higher levels of acidity. Viruses with these mutations and others that enabled them to bind to different receptors were able to replicate more efficiently in ferrets and spread from one animal to another.

The results have important implications for designing vaccines against potential pandemic strains of bird flu. Live attenuated flu vaccines (LAIV) might be used in a pandemic situation because it is possible to manufacture many more doses of this type of vaccine than of the killed virus vaccines used to protect against seasonal flu. LAIV are based on weakened viruses that don’t cause illness, but they still have to replicate in order to elicit a strong immune response. Viruses with modified haemagglutinin proteins induced strong antibody responses in ferrets in this study, suggesting that vaccines with similar modifications might prove more effective than those tested previously.

“We can’t predict how bird flu viruses will evolve in the wild, but the more we understand about the kinds of mutations that will enable them to transmit between humans, the better we can prepare for a possible pandemic,” said Professor Barclay.

The research was funded by the Medical Research Council and the Wellcome Trust and published in the Journal of General Virology.

Reference

H Shelton et al. ‘Mutations in hemagglutinin that affect receptor binding and pH stability increase replication of a PR8 influenza virus with H5 HA in the upper respiratory tract of ferrets and may contribute to transmissibility.’ Journal of General Virology (2013) doi:10.1099/vir.0.050526-0

http://www3.imperial.ac.uk/newsandeventspggrp/imperialcollege/newssummary/news_8-4-2013-12-47-4

 

Researchers are first to use common virus to ‘fortify’ adult stem cells: “Basically, we’ve helped the cells be ‘invisible’ to the body’s natural killer cells, T cells and other aspects of the immune system”

Contact: Karen Richardson krchrdsn@wakehealth.edu 336-716-4453 Wake Forest Baptist Medical Center

Researchers are first to use common virus to ‘fortify’ adult stem cells

Potential uses of engineered cells include organ transplant and brain injury

WINSTON-SALEM, N.C. – April 1, 2013 – Using the same strategy that a common virus employs to evade the human immune system, researchers at Wake Forest Baptist Medical Center’s Institute for Regenerative Medicine have modified adult stem cells to increase their survival – with the goal of giving the cells time to exert their natural healing abilities.

“Basically, we’ve helped the cells be ‘invisible’ to the body’s natural killer cells, T cells  and other aspects of the immune system, so they can survive to promote healing,” said Graca Almeida-Porada, M.D., Ph.D., senior author and professor of regenerative medicine at Wake Forest Baptist.

The research, reported in the current issue of PLOS One, a peer-reviewed, open access journal, involves mesenchymal stem cells (MSCs), found in bone marrow, peripheral and cord blood and fetal liver and lung tissue. These cells are known for their ability to migrate to damaged tissues and contribute to healing. However, like all cells, they are susceptible to being killed by the body’s complement system, a part of the immune system involved in inflammation and organ rejection.

“These cells have a natural ability to help modulate the immune response, so if we can increase their survival, they theoretically could be a therapy to decrease inflammation and help transplant patients avoid organ rejection,” said Almeida-Porada.

In the study, the researchers evaluated the potential of human cytomegalovirus (HCMV), a member of the herpes virus family, to help increase the survival of MSCs. While the HCMN virus infects between 50 percent and 80 percent of people in the U.S., it normally produces no symptoms and remains latent in the body over long periods.

“We wanted to take advantage of the virus’ ability to evade the immune system,” said Almeida-Porada. “Our strategy was to modify the cells to produce the same proteins as the HCMV virus so they could escape death and help modulate inflammation and promote healing.”

MSCs were purified from human fetal liver tissue. They were then engineered to produce specific proteins expressed by the HMCV virus. Through this process, the scientists identified the protein that was most effective at increasing cell survival. Specifically, the team is the first to show that overexpression of the US2 protein made the cells less recognizable to the immune system and increased cell survival by 59 percent (+/- 13 percent).

“The research showed that modifying the cells indeed improves their survival,” said Almeida-Porada. “Next, we hope to evaluate the healing potential of these cells in conditions such as bowel disease, traumatic brain injury and human organ transplant.”

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The research was supported by National Institutes of Health grants HL73737 and HL97623.

Almeida-Porada’s co-researchers were Melisa A. Soland, Ph.D., and Christopher Porada, Ph.D., Wake Forest Baptist; Mariana Bego, Ph.D., Institut de Recherches Cliniques de Montreal, Canada; and Evan Colletti, Ph.D, Esmail Zanjani, Ph.D., and Stephen S. Jeor, Ph.D., University of Nevada.

Media contacts:

Karen Richardson Media Relations Office 336-716-4587.

Wake Forest Baptist Medical Center is a fully integrated academic medical center located in Winston-Salem, North Carolina. The institution comprises the medical education and research components of Wake Forest School of Medicine, the integrated clinical structure and consumer brand Wake Forest Baptist Health, which includes North Carolina Baptist Hospital and Brenner Children’s Hospital, the creation and commercialization of research discoveries into products that benefit patients and improve health and wellness, through Wake Forest Innovations, Wake Forest Innovation Quarter, a leading center of technological discovery, development and commercialization, as well as a network of affiliated community-based hospitals, physician practices, outpatient services and other medical facilities. Wake Forest School of Medicine is ranked among the nation’s best medical schools and is a leading national research center in fields such as regenerative medicine, cancer, neuroscience, aging, addiction and public health sciences. Wake Forest Baptist’s clinical programs have consistently ranked as among the best in the country by U.S. News & World Report for the past 20 years.

The first caffeine-‘addicted’ bacteria

Contact: Michael Bernstein m_bernstein@acs.org 202-872-6042 American Chemical Society

Some people may joke about living on caffeine, but scientists now have genetically engineered E. coli bacteria to do that — literally. Their report in the journal ACS Synthetic Biology describes bacteria being “addicted” to caffeine in a way that promises practical uses ranging from decontamination of wastewater to bioproduction of medications for asthma.

Jeffrey E. Barrick and colleagues note that caffeine and related chemical compounds have become important water pollutants due to widespread use in coffee, soda pop, tea, energy drinks, chocolate and certain medications. These include prescription drugs for asthma and other lung diseases. The scientists knew that a natural soil bacterium, Pseudomonas putida CBB5, can actually live solely on caffeine and could be used to clean up such environmental contamination. So they set out to transfer genetic gear for metabolizing, or breaking down, caffeine from P. putida into that old workhorse of biotechnology, E. coli, which is easy to handle and grow.

The study reports their success in doing so, as well as use of the E. coli for decaffeination and measuring the caffeine content of beverages. It describes development of a synthetic packet of genes for breaking down caffeine and related compounds that can be moved easily to other microbes. When engineered into certain E. coli, the result was bacteria literally addicted to caffeine. The genetic packet could have applications beyond environmental remediation, the scientists say, citing potential use as a sensor to measure caffeine levels in beverages, in recovery of nutrient-rich byproducts of coffee processing and for the cost-effective bioproduction of medicines.

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The author and co-authors acknowledge financial support from the University of Texas at Austin and the University of Iowa.

The American Chemical Society is a nonprofit organization chartered by the U.S. Congress. With more than 163,000 members, ACS is the world’s largest scientific society and a global leader in providing access to chemistry-related research through its multiple databases, peer-reviewed journals and scientific conferences. Its main offices are in Washington, D.C., and Columbus, Ohio.

To automatically receive news releases from the American Chemical Society, contact newsroom@acs.org.

 

Vial containing strain of potentially deadly virus missing from Texas laboratory

By  Daily Mail Reporter

PUBLISHED: 18:20 EST, 24  March 2013 |  UPDATED: 18:20 EST, 24 March 2013

 

A small vial containing a potentially harmful  strain of virus has gone missing from a Texas laboratory, it was revealed  today.

The vial, which contains a strain of the  Guanarito virus, had been locked in a bio-hazard freezer within the University  of Texas’ Medical Branch campus.

The strain of virus is part of a family of  diseases that caused deadly outbreaks in Venezuela and could cause hemorrhagic  fever.

k 

A small vial containing a potentially harmful strain of  virus has gone missing from a Texas laboratory (file photo)

Officials at the UTMB noticed that a single  vial of the substance was missing from the freezer early last week,  the Houston Chronicle reported.

UTMB director Scott Weaver told the paper  that Guanarito has been responsible for causing deadly diseases within the South  American country.

Government officials have made studying the  strain a priority as it can potentially be used by terrorists in a contagion  attack.

Upon discovery that one out of the five vials  at the lab was missing, officials contacted the Centers for Disease Control and  Prevention.

They said that there was no security breach  or break-in at the Texas facility, nor was there any suspicion of foul play.

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The vial was housed at the University of Texas Medical  Branch in Galveston; officials believe there was no foul play and that the vial  could have simply broken in the lab’s cleaning process

Officials further added that they believe the  vial could have been accidentally destroyed during the lab’s cleaning  process.

The virus is transmitted through contact with  infected Venezuelan rats, but scientists do not believe it can survive on U.S.  rats.

Read more: http://www.dailymail.co.uk/news/article-2298596/Vial-containing-strain-potentially-deadly-virus-missing-Texas-laboratory.html#ixzz2OVxn2OMz Follow us: @MailOnline on Twitter | DailyMail on Facebook

Contaminated water used to dilute pesticides could be responsible for viruses entering the food chain, warn scientists

Contact: Sacha Boucherie S.Boucherie@elsevier.com 31-204-853-564 Elsevier

Pesticide application as potential source of noroviruses in fresh food supply chains

Human norovirus (hNoV), also known as the winter vomiting bug, is one of the most common stomach bugs in the world. The virus is highly contagious, causing vomiting and diarrhea, and the number of affected cases is growing. Currently there is no cure; sufferers have to let the virus run its course for a few days.

The consumption of fresh produce is frequently associated with outbreaks of hNoV but it remains difficult to identify where in the supply chain the virus first enters production.

A new study, published in the International Journal of Food Microbiology investigated whether contaminated water used to dilute pesticides could be a source of hNoV. Farmers use various water sources in the production of fresh fruits and vegetables, including well water and different types of surface water such as river water or lake water – sources which have been found to harbour hNoV.

To test this theory, eight different pesticides were analyzed in the study; each was diluted with hNoV contaminated water. The researchers tested whether traces of the virus were present in the samples after the two elements were combined. Results showed that the infectivity of the norovirus was unaffected when added to the pesticide samples. In other words: pesticides did not counteract the effects of the contaminated water.

The authors conclude that the application of pesticides on fresh produce may not only be a chemical hazard, but may in fact also be a microbiological risk factor; both having consequences on public health.

###

Notes for editors

This article is “Persistence of human norovirus in reconstituted pesticides — Pesticide application as a possible source of viruses in fresh produce chains” by Katharina Verhaelen, Martijn Bouwknegt, Saskia A. Rutjes and Ana Maria de Roda Husman  (DOI: 10.1016/j.ijfoodmicro.2012.11.007) and appears in International Journal of Food Microbiology published by Elsevier.

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Cancer vaccines self-sabotage, channel immune attack to injection site

 

UT MD Anderson scientists find common vaccine ingredient diverts T cells from tumors

HOUSTON – Cancer vaccines that attempt to stimulate an immune system assault fail because the killer T cells aimed at tumors instead find the vaccination site a more inviting target, scientists at The University of Texas MD Anderson Cancer Center report in Nature Medicine.

A common substance used in many cancer vaccines to boost immune attack betrays the cause by facilitating a buildup of T cells at the vaccination site, which then summon more T cells to help with the perceived threat.

“Vaccines stimulate production of T cells primed to attack the target cancer, and there are many T cells in the bloodstream after vaccination.  We found that only a few get to the tumor while many more are stuck at or double back to the vaccination site,” said senior author Willem Overwijk,  Ph.D., in MD Anderson’s Department of Melanoma Medical Oncology.

The result: largely unscathed tumors while an overstimulated immune response can cause lesions at the injection site. The team found that a major culprit in this failure is incomplete Freund’s adjuvant (IFA), a mineral oil-based adjuvant included in many vaccines to stoke the immune response.

“IFA sticks around the vaccination site for up to three months, along with the antigen designed to trigger immunity against the tumor,” Overwijk said. “T cells keep attacking and secreting chemokines to call for reinforcements.  But it’s an unkillable target; T cells can’t kill mineral oil.”

Eventually, the T cells die. “The vaccination site increasingly resembles a viral infection, with lots of damaged tissue and antigens,” Overwijk said.

Switch from IFA to saline adjuvant reverses effect

“Switching to a saline-based adjuvant in a melanoma vaccine reversed the T cell effect in mice,” Overwijk said, “Major accumulations of T cells gathered in tumors, shrinking them, with minimal T cell activity at the vaccination site.”

Peptide antigens are available for almost all types of cancer, Overwijk said. A saline adjuvant could change the poor performance of cancer vaccines.

A clinical trial of the concept is expected to open later this year led by Craig Singluff Jr., M.D., professor of surgery at the University of Virginia Medical School, and Patrick Hwu, M.D., chair of MD Anderson’s Department of Melanoma Medical Oncology.

Overwijk and colleagues noted 98 federally approved U.S. clinical trials of vaccines against a variety of cancers have almost all failed, while another 37 trials are open, enrolling patients. The U.S. Food and Drug Administration has approved only one therapeutic vaccine, for treatment of prostate cancer, out of all of those trials.

“Our group and many other researchers have been trying for years to improve the performance of cancer vaccines, to no avail,” Overwijk said. “People kept trying because of these beguiling T cell levels in the blood. But our data suggest that the very nature of IFA-based vaccines may make it almost impossible for them to work well.”

In past experiments and clinical trials, tumors were rarely examined for evidence of T cell penetration.  In people, they are often inoperable, and there was no indication that it needed to be done.  “But a few researchers did analyze human tumors for T cell infiltration and largely found what we found in our mouse experiments,” he said.

Mouse studies reveal vaccine self-sabotage

The team studied the fate of melanoma-specific CD8-positive T cells after vaccination with the gp100 peptide with and without IFA.

Both vaccines increased levels of the desired T cells in the blood, but with IFA, the T cells dropped to nearly undetectable levels after three weeks and did not rebound even with an engineered virus-based booster.  The vaccine-lacking IFA produced similar peak amounts of the T cells, a response that persisted over time.

The research team fluorescently tagged T cells in the mouse model to see where they went.

  • Mice without IFA had the bulk of T cells light up in their tumors with minimal presence at the vaccination site.
  • T cells built up at the injection site in mice that received IFA-based vaccine, with a tiny showing in the tumor.

 

Response duration was tested in gp100/IFA and control IFA vaccines. The antigen/IFA combination gathered and persisted at the vaccination site, where it could still stimulate the proliferation of injected T cells 96 days after vaccination.

A separate set of experiments showed the antigen/IFA-driven T cells were forced to kill themselves at the vaccination site by a variety of cell suicide-inducing proteins.

Reducing vaccine depots at injection site

Overwijk and colleagues inferred that a possible answer to the problem was to reduce the size and persistence of vaccine “depots” at the injection site.

They tested a vaccine based on a saline solution instead of IFA and found that antigens cleared more quickly but did not spark the desired T cell response.  A combination of three stimulatory molecules (covax) was added to the saline/peptide vaccine, producing a strong T cell response.  IFA/peptide vaccine produced a strong T cell response but also stronger post-peak T cell suicide.

A comparison of saline/peptide/covax vs. IFA/peptide/covax showed the saline version caused T cells to home to the tumor and destroy them, while the IFA version focused T cells at the vaccination site, killing normal tissue and inducing chemokines that damaged and killed T cells.

“IFA-based vaccination sites essentially outcompete tumor sites for T cell recognition and accumulation, chemokine production and tissue damage,” Overwijk said. “It’s an engineering flaw in those vaccines that we didn’t appreciate until now. Fortunately, our results also directly instruct us how to design new, more powerful vaccine formulas for treating people with cancer.”

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Co-authors are first author Yared Hailemichael, Zhimin Dai, Nina Jaffarzad, Yang Ye, Miguel Medina, Xue-Fei Huang, Stephanie Dorta-Estremera Nathaniel Greeley, , Giovanni Nitti, Weiyi Peng, Chengwen Liu, Yanyan Lou, Brian Rabinovich and Patrick Hwu, all of MD Anderson’s Department of Melanoma Medical Oncology; Zhiqiang Wang, Wencai Ma, and Richard Davis, of MD Anderson’s Department of Lymphoma and Myeloma; and Kimberly Schluns,  of MD Anderson’s Department of Immunology.

Dorta-Estremera, Greeley, and Nitti are graduate students in The University of Texas Graduate School of Biomedical Sciences, a graduate school operated jointly by MD Anderson and The University of Texas Health Science Center at Houston. Schluns, Davis, Hwu and Overwijk also are on the GSBS faculty.

Grants from the National Cancer Institute of the National Institutes of Health (RO1 1CA143077 and PO1 CA128913) and an award from the Melanoma Research Alliance funded this research.

 

About MD Anderson

The University of Texas MD Anderson Cancer Center in Houston ranks as one of the world’s most respected centers focused on cancer patient care, research, education and prevention. MD Anderson is one of only 41 comprehensive cancer centers designated by the National Cancer Institute. For nine of the past 11 years, including 2012, MD Anderson has ranked No. 1 in cancer care in “America’s Best Hospitals,” a survey published annually in U.S. News & World Report.  MD Anderson receives a cancer center support grant from the National Cancer Institute of the National Institutes of Health (P30 CA016672).

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‘Defective’ virus surprisingly plays major role in spread of disease, UCLA life scientists report

Contact: Stuart Wolpert swolpert@support.ucla.edu 310-206-0511 University of California – Los Angeles

Defective viruses, thought for decades to be essentially garbage unrelated to the transmission of normal viruses, now appear able to play an important role in the spread of disease, new research by UCLA life scientists indicates.

Defective viruses have genetic mutations or deletions that eliminate their essential viral functions. They have been observed for many human pathogens and are generated frequently for viruses that have high mutation rates. However, for some 40 years, it was believed that they were unimportant in natural settings.

In findings published Feb. 28 in the journal PLoS Pathogens, UCLA scientists and their colleagues report for the first time a significant link between a defective virus and an increased rate of transmission of a major disease.

“The idea has always been that defective viruses are either meaningless or detrimental,” said James O. Lloyd-Smith, a UCLA assistant professor of ecology and evolutionary biology and the senior author of the research. “We have found the opposite of that — that the defective virus is actually helping the normal, functional virus. This finding is bizarre and hard to believe, but the data are the data.”

“We have shown that the defective virus not only transmits with the virus but increases the transmission of the functional virus,” said Ruian Ke, a UCLA postdoctoral scholar in the department of ecology and evolutionary biology and the lead author of the study.

Defective viruses cannot complete their life cycle on their own, but if they’re able to get into the same cell with a non-defective virus, they can “hitchhike” with the normal virus and propagate, Lloyd-Smith said. Biologists had thought that defective viruses interfered with normal versions of the virus, “clogging up the gears of viral replication,” he said.

The life scientists studied DENV-1, one of four known types of the dengue virus that infect humans. Dengue viruses are transmitted by several species of mosquitoes and cause dengue fever, which is characterized by fever, joint pain and a skin rash similar to measles. Dengue hemorrhagic fever, a more severe form of dengue infection, can cause death. The dengue virus infects between 50 million and 100 million people each year in Southeast Asia, South America, parts of the United States and elsewhere.

The life sciences team — which also included John Aaskov, a virologist and professor of health at Australia’s Queensland University of Technology in Brisbane, and Edward Holmes, a professor of biological sciences at Australia’s University of Sydney — found that the presence of a defective DENV-1 virus may have led to large increases in dengue fever cases in Myanmar in 2001 and 2002, when that country experienced its most severe dengue epidemics on record.

The scientists describe when and how the defective “lineage,” or series of very closely related defective DENV-1 viruses, emerged and was transmitted between humans and mosquitoes in Myanmar, as well as what the public health implications are.

For the study, Ke designed a mathematical model to analyze the data to learn how the defective DENV-1 virus interacted with the normal virus. Aaskov and Holmes collected genetic sequences from from 15 people in Myanmar sampled over an 18-month period, all of whom were infected with the DENV-1 virus and nine of whom were also infected with the defective version.

Ke discovered that the lineage of defective viruses emerged between June 1998 and February 2001 and that it was spreading in the population until at least 2002. (The following year, the lineage appeared on the South Pacific island of New Caledonia, carried there by either a mosquito or a person.) The scientists analyzed the genetic sequences of both the defective and normal dengue viruses to estimate how long the defective virus had been transmitting in the human population.

“We can see from the gene sequence of the defective version that it is the same lineage and is a continued propagation of the virus,” said Lloyd-Smith, who holds UCLA’s De Logi Chair in Biological Sciences. “From 2001 to 2002, it went from being quite rare to being in all nine people we sampled that year; everybody sampled who was getting dengue fever was getting the defective version along with the functional virus. It rose from being rare to being very common in just one year.”

Most surprisingly, Lloyd-Smith said, the combination of the defective virus with the normal virus was “more fit” than the normal dengue virus alone.

“What we have shown is that this defective virus, which everyone had thought was useless or even detrimental to the fitness of the functional virus, actually appears to have made it better able to spread,” he said. “Ruian [Ke] calculated that the defective virus makes it at least 10 percent more transmissible, which is a lot. It was spreading better with its weird, defective cousin tagging along than on its own.

“This study has shown that the functional virus and defective virus travel in unison. The two transmit together in an unbroken chain, and that’s not just a matter of getting into the same human or the same mosquito — they need to get into the same cell inside that human or mosquito in order to share their genes and for the defective version to continue ‘hitchhiking.’ We are gaining insights into the cellular-level biology of how dengue is infecting hosts. It must be the case that frequently there are multiple infections of single cells.

“Ruian showed the defective virus appeared one to three years before these major epidemics,” Lloyd-Smith added. “One could imagine that if you build an understanding of this mechanism, you could measure it, see it coming and potentially get ahead of it.”

Might defective viruses play a role in the transmission of influenza, measles and other diseases?

“There are a few signs that this phenomenon may be happening for other viruses,” Lloyd-Smith said. “We may be cracking open the book on the possible interactions between the normal, functional viruses and the defective ones that people thought were just dead-ends. These supposedly meaningless viruses may be having a positive impact — positive for the virus, not for us. There is great variation, year to year, in how large dengue epidemics are in various locations, and we don’t understand why. This is a possible mechanism for why there are large epidemics in some years in some places. We need to keep studying this question.”

The research points to implications for how mutations might allow a new non-human virus to become a human virus.

“Different strains of a virus with different genetic properties may be interacting more frequently than we thought,” said Lloyd-Smith, who studies how ecology, evolution and epidemiology merge to drive the emergence of new pathogens, including new strains with important properties like drug resistance.

Why would a defective virus increase transmission of a disease?

Lloyd-Smith offers two hypotheses. One is that the presence of the defective virus with the functional virus in the same cell makes the functional virus replicate better within the cell by some unknown mechanism. “It might give the virus a bit of flexibility in how it expresses its genes and may make it a bit more fit, a bit better able to reproduce under some circumstances,” he said.

A second idea is that the defective virus may be interfering with the disease-causing virus, making the disease less intense; people then have a milder infection, and because they don’t feel as sick, they are more likely to go out and spread the disease.

“Normally, biologists test for how well a virus can replicate in a cell, but what we have shown here is even a genotype that cannot replicate in a cell can have an impact on transmission,” Ke said.

In conducting the research, Lloyd-Smith and Ke combined genetic sequence analysis with sophisticated mathematical models and bioinformatics.

Genetic sequencing technology has “exploded,” Lloyd-Smith said, providing a wealth of data on genetic sequences of pathogens and the evolution of viruses, leading to major new insights into the transmission of viruses.

“We were able to show that this defective virus transmitted in an unbroken chain across this population for a year-and-a-half,” Lloyd-Smith said. “Without gene sequencing, we would not have been able to establish that.”

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The research was federally funded by the National Science Foundation.

Read more about Lloyd-Smith’s research.

UCLA is California’s largest university, with an enrollment of more than 40,000 undergraduate and graduate students. The UCLA College of Letters and Science and the university’s 11 professional schools feature renowned faculty and offer 337 degree programs and majors. UCLA is a national and international leader in the breadth and quality of its academic, research, health care, cultural, continuing education and athletic programs. Six alumni and six faculty have been awarded the Nobel Prize.

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Mutation altering stability of surface molecule in acid enables H5N1 infection of mammals

Contact: Jim Sliwa jsliwa@asmusa.org 202-942-9297 American Society for Microbiology

A single mutation in the H5N1 avian influenza virus that affects the pH at which the hemagglutinin surface protein is activated simultaneously reduces its capacity to infect ducks and enhances its capacity to grow in mice according to research published ahead of print today in the Journal of Virology.

“Knowing the factors and markers that govern the efficient growth of a virus in one host species, tissue, or cell culture versus another is of fundamental importance in viral infectious disease,” says Charles J. Russell of St. Jude Children’s Research Hospital, Memphis, TN, an author on the study. “It is essential for us to identify influenza viruses that have increased potential to jump species, to help us make decisions to cull animals, or quarantine humans.” The same knowledge “will help us identify targets to make new drugs that stop the virus… [and] engineer vaccines.”

Various influenza viruses are spreading around the globe among wild birds, but fortunately, few gain the ability to jump to humans. However, those that do, and are able to then spread efficiently from person to person, cause global epidemics, such as the infamous pandemic of 1918, which infected one fifth and killed an estimated 2.7 percent of the world’s population. Occasionally, one of these viruses is exceptionally lethal. For example, H5N1 has killed more than half of the humans it has infected. The specter of such a virus becoming easily transmissible among humans truly frightens public health officials. But understanding the mechanisms of transmission could help microbiologists find ways to mitigate major epidemics.

When influenza viruses infect birds, the hemagglutinin surface protein of the virus is activated by acid in the entry pathway inside the host cell, enabling it to invade that cell. In earlier work, Russell and collaborators showed that a mutant version of the influenza H5N1 virus called K58I that resists acid activation, loses its capacity to infect ducks. Noting that the upper airways of mammals are more acidic than infected tissues of birds, they hypothesized, correctly, that a mutation rendering the hemagglutinin protein resistant to acid might render the virus more infective in mammals.

In this study the investigators found that K58I grows 100-fold better than the wild-type in the nasal cavities of mice, and is 50 percent more lethal. Conversely, the mutant K58I virus failed completely to kill ducks the investigators infected, while the wild-type killed 66 percent of ducks, says Russell. “A single mutation that eliminates H5N1 growth in ducks simultaneously enhances the capacity of H5N1 to grow in mice. We conclude that enhanced resistance to acid inactivation helps adapt H5N1 influenza virus from an avian to a mammalian host.”

“These data contribute new information about viral determinants of influenza virus virulence and provide additional evidence to support the idea that H5N1 influenza virus pathogenesis in birds and mammals is linked to the pH of [hemagglutinin] activation in an opposing fashion,” Terence S. Dermody of Vanderbilt University et al. write in an editorial in the journal accompanying the paper. “A higher pH optimum of [hemagglutinin] activation favors virulence in birds, whereas a lower pH optimum… favors virulence in mammals.”

Based on this and another study, “…surveillance should include phenotypic assessment of the [hemagglutinin] activation pH in addition to sequence analysis,” Dermody writes.

The journal carefully considered whether to publish the paper, because it raised issues of “dual use research of concern” (DURC), writes Dermody. DURC is defined as “Life sciences research that, based on current understanding, can be reasonably anticipated to provide knowledge, information, products, or technologies that could be directly misapplied to pose a significant threat with broad potential consequences to public health and safety, agricultural crops and other plants, animals, the environment, materiel, or national security,” according to a US government policy document. However, both the National Institute of Allergy and Infectious Diseases and the St. Jude Institutional Biosafety Committee concluded that the study failed to meet the definition of DURC. Clinching the case, “the addition of the key mutation in the Russell paper to other previously reported mutations would not result in an even more virulent H5N1 influenza virus,” says Dermody.

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A copy of the research manuscript can be found online at http://bit.ly/asmpr0213b.  The manuscript of the accompanying editorial can be accessed at http://bit.ly/asmpr0213c. Both are scheduled to be formally published in the May 2013 issue of the Journal of Virology.

(H. Zaraket, O.A. Bridges, and C.J. Russell, 2013. The pH of activation of the hemagglutinin protein regulates H5N1 influenza virus replication and pathogenesis in mice. J. Virol. online ahead of print February 28, 2013, doi:10.1128/JVI.03110-12.)

The Journal of Virology is a publication of the American Society for Microbiology (ASM).  The ASM is the largest single life science society, composed of over 39,000 scientists and health professionals. Its mission is to advance the microbiological sciences as a vehicle for understanding life processes and to apply and communicate this knowledge for the improvement of health and environmental and economic well-being worldwide.

Increased risk of sleep disorder in children who received swine flu vaccine : Up to 16-fold increased risk

Contact: Emma Dickinson edickinson@bmjgroup.com 44-020-738-36529 BMJ-British Medical Journal

Results consistent with findings from Finland and Sweden, but may still be overestimated

The results are consistent with previous studies from Finland and Sweden and indicate that the association is not confined to Scandinavian populations. However, the authors stress that the risk may still be overestimated, and they call for longer term monitoring of the cohort of children and adolescents exposed to Pandemrix to evaluate the exact level of risk.

In 2009, pandemic influenza A (H1N1) virus spread rapidly, resulting in millions of cases and over 18,000 deaths in over 200 countries. In England the vaccine Pandemrix was introduced in October 2009. By March 2010, around one in four (24%) of healthy children aged under 5 and just over a third (37%) aged 2-15 in a risk group had been vaccinated.

In August 2010 concerns were raised in Finland and Sweden about a possible association between narcolepsy and Pandemrix. And in 2012 a study from Finland reported a 13-fold increased risk in children and young people aged 4-19.

But a lack of reported cases in other countries led to speculation that any possible association might be restricted to these Scandinavian populations.

Narcolepsy is a chronic disorder of excessive daytime sleepiness, often accompanied by sudden muscle weakness triggered by strong emotion (known as cataplexy). To evaluate the risk after vaccination in England, a team of researchers reviewed case notes for 245 children and young people aged 4-18 from sleep centres and child neurology centres across England.

Of these, 75 had narcolepsy (56 with cataplexy) with onset after 1 January 2008. Eleven had been vaccinated before onset of symptoms; seven within six months.

After adjusting for clinical conditions, vaccination at any time was associated with a 14-fold increased risk of narcolepsy, whereas vaccination within six months before onset was associated with a 16-fold increased risk.

In absolute numbers, this means that one in 52,000 to 57,500 doses are associated with narcolepsy, say the authors.

They write: “The increased risk of narcolepsy after vaccination with ASO3 adjuvanted pandemic A/H1N1 2009 vaccine indicates a causal association, consistent with findings from Finland. Because of variable delay in diagnosis, however, the risk might be overestimated by more rapid referral of vaccinated children.”

While further use of this vaccine for prevention of seasonal flu seems unlikely, they say their findings “have implications for the future licensure and use of AS03 adjuvanted pandemic vaccines containing different subtypes such H5 or H9.”

And they conclude: “Further studies to assess the risk, if any, associated with the other A/H1N1 2009 vaccines used in the pandemic, including those with and without adjuvants, are also needed to inform the use of such vaccines in the event of a future pandemic.”

Liver cancer survival time tripled by virus: JX-594

The virus used in the vaccine that helped eradicate smallpox is now working its magic on liver cancer. A genetically engineered version of the vaccinia virus has trebled the average survival time of people with a severe form of liver cancer, with only mild, flu-like side effects.Thirty people with hepatocellular carcinoma received three doses of the modified virus – code-named JX-594 – directly into their liver tumour over one month. Half the volunteers received a low dose of the virus, the other half a high dose. Members of the low and high-dose groups subsequently survived for, on average, 6.7 and 14.1 months respectively. By contrast, trials several years ago showed that sorafenib, the best existing medication for this cancer, prolonged life by only three months.

Two of the patients on the highest viral dose were still alive more than two years after the treatment. “It’s a very substantial survival benefit,” says Laurent Fischer, president of Jennerex, the company in San Francisco developing the treatment under the trade name Pexa-Vec.

Besides shrinking the primary tumour, the virus was able to spread to and shrink any secondary tumours outside the liver. “Some tumours disappeared completely, and most showed partial destruction on MRI scans,” says David Kirn, head of the study at Jennerex. Moreover, the destruction was equally dramatic in the primary and secondary tumours.

“This clinical trial is an exciting step forward to help find a new way of treating cancers,” says Alan Melcher of the University of Leeds, UK, who was not involved in the study. “It helps demonstrate the cancer-fighting potential of viruses, which have relatively few side effects compared with traditional chemo or radiotherapy,” he says. “If it proves effective in larger trials, it could be available to patients within five years.”

The fact that the virus appears able to spread to secondary tumours suggests that simply injecting the virus into the bloodstream may be effective. A trial to compare this treatment with injecting the virus directly into a tumour is under way.

Targeted at cancer

The virus has had a gene coding for an enzyme called thymidine kinase snipped out. The enzyme enables the virus to recognise and infect dividing cells. By removing the gene, the virus’s developers have reduced the likelihood of healthy dividing cells being infected.

Instead, the virus exclusively attacks cancerous tissue, by targeting two genes that have increased activity in tumour cells. One genes is associated with an epidermal growth factor receptor, which stimulates the cancer to grow. The other is associated with a vascular endothelial growth factor, which enables the cancer to recruit its own blood supply. The virus reduces the activity of both genes, causing the infected cancer cell to wither and die.

What’s more, the virus carries extra genes to prod the body’s own immune system into action against the cancer. One produces granulocyte colony stimulating factor, a protein that encourages production of extra white blood cells at sites of infection. The other produces a protein not naturally found in humans, called Lac-Z, that earmarks infected cells for destruction.

Fischer says that to date, more than 200 people have received the virus, which has also shown promise against other types of cancer, including those of the kidney and skin. But he warns that not everyone sees a benefit. “We know why patients respond, but not why they don’t,” he says.

Journal reference: Nature Medicine, DOI: 10.1038/nm.3089

http://www.newscientist.com/article/dn23154-liver-cancer-survival-time-tripled-by-virus.html

 

Insight: Evidence grows for narcolepsy link to GSK swine flu shot : Doctors are fearful of having their reputations ruined by reporting possible links

By Kate Kelland, Health and Science Correspondent | Reuters – 8 mins ago

STOCKHOLM (Reuters) – Emelie is plagued by hallucinations and nightmares. When she wakes up, she’s often paralyzed, unable to breathe properly or call for help. During the day she can barely stay awake, and often misses school or having fun with friends. She is only 14, but at times she has wondered if her life is worth living.

Emelie is one of around 800 children in Sweden and elsewhere in Europe who developed narcolepsy, an incurable sleep disorder, after being immunized with the Pandemrix H1N1 swine flu vaccine made by British drugmaker GlaxoSmithKline in 2009.

Finland, Norway, Ireland and France have seen spikes in narcolepsy cases, too, and people familiar with the results of a soon-to-be-published study in Britain have told Reuters it will show a similar pattern in children there.

Their fate, coping with an illness that all but destroys normal life, is developing into what the health official who coordinated Sweden’s vaccination campaign calls a “medical tragedy” that will demand rising scientific and medical attention.

Europe’s drugs regulator has ruled Pandemrix should no longer be used in people aged under 20. The chief medical officer at GSK’s vaccines division, Norman Begg, says his firm views the issue extremely seriously and is “absolutely committed to getting to the bottom of this”, but adds there is not yet enough data or evidence to suggest a causal link.

Others – including Emmanuel Mignot, one of the world’s leading experts on narcolepsy, who is being funded by GSK to investigate further – agree more research is needed but say the evidence is already clearly pointing in one direction.

“There’s no doubt in my mind whatsoever that Pandemrix increased the occurrence of narcolepsy onset in children in some countries – and probably in most countries,” says Mignot, a specialist in the sleep disorder at Stanford University in the United States.

30 MILLION RECEIVED PANDEMRIX

In total, the GSK shot was given to more than 30 million people in 47 countries during the 2009-2010 H1N1 swine flu pandemic. Because it contains an adjuvant, or booster, it was not used in the United States because drug regulators there are wary of adjuvanted vaccines.

GSK says 795 people across Europe have reported developing narcolepsy since the vaccine’s use began in 2009.

Questions about how the narcolepsy cases are linked to Pandemrix, what the triggers and biological mechanisms might have been, and whether there might be a genetic susceptibility are currently the subject of deep scientific investigation.

But experts on all sides are wary. Rare adverse reactions can swiftly develop into “vaccine scares” that spiral out of proportion and cast what one of Europe’s top flu experts calls a “long shadow” over public confidence in vaccines that control potential killers like measles and polio.

“No-one wants to be the next Wakefield,” said Mignot, referring to the now discredited British doctor Andrew Wakefield who sparked a decades-long backlash against the measles, mumps and rubella (MMR) shot with false claims of links to autism.

With the narcolepsy studies, there is no suggestion that the findings are the work of one rogue doctor.

Independent teams of scientists have published peer-reviewed studies from Sweden, Finland and Ireland showing the risk of developing narcolepsy after the 2009-2010 immunization campaign was between seven and 13 times higher for children who had Pandemrix than for their unvaccinated peers.

“We really do want to get to the bottom of this. It’s not in anyone’s interests if there is a safety issue that needs to be addressed,” said GSK’s Begg.

LIFE CHANGED

Emelie’s parents, Charles and Marie Olsson, say she was a top student who loved playing the piano, taking tennis lessons, creating art and having fun with friends. But her life started to change in early 2010, a few months after she had Pandemrix. In the spring of 2010, they noticed she was often tired, needing to sleep when she came home from school.

But it wasn’t until May, when she began collapsing at school, that it became clear something serious was happening.

As well as the life-limiting bouts of daytime sleepiness, narcolepsy brings nightmares, hallucinations, sleep paralysis and episodes of cataplexy – when strong emotions trigger a sudden and dramatic loss of muscle strength.

In Emelie’s case, having fun is the emotional trigger. “I can’t laugh or joke about with my friends anymore, because when I do I get cataplexies and collapse,” she said in an interview at her home in the Swedish capital.

Narcolepsy is estimated to affect between 200 and 500 people per million and is a lifelong condition. It has no known cure and scientists don’t really know what causes it. But they do know patients have a deficit of a brain neurotransmitter called orexin, also known as hypocretin, which regulates wakefulness.

Research has found that some people are born with a variant in a gene known as HLA that means they have low hypocretin, making them more susceptible to narcolepsy. Around 25 percent of Europeans are thought to have this genetic vulnerability.

When results of Emelie’s hypocretin test came back in November last year, it showed she had 15 percent of the normal amount, typical of heavy narcolepsy with cataplexy.

The seriousness of her strange new illness has forced her to contemplate life far more than many other young teens: “In the beginning I didn’t really want to live any more, but now I have learned to handle things better,” she said.

TRIGGERS?

Scientists investigating these cases are looking in detail at Pandemrix’s adjuvant, called AS03, for clues.

Some suggest AS03, or maybe its boosting effect, or even the H1N1 flu itself, may have triggered the onset of narcolepsy in those who have the susceptible HLA gene variant.

Angus Nicoll, a flu expert at the European Centre for Disease Prevention and Control (ECDC), says genes may well play a part, but don’t tell the whole story.

“Yes, there’s a genetic predisposition to this condition, but that alone cannot explain these cases,” he said. “There was also something to do with receiving this specific vaccination. Whether it was the vaccine plus the genetic disposition alone or a third factor as well – like another infection – we simply do not know yet.”

GSK is funding a study in Canada, where its adjuvanted vaccine Arepanrix, similar to Pandemrix, was used during the 2009-2010 pandemic. The study won’t be completed until 2014, and some experts fear it may not shed much light since the vaccines were similar but not precisely the same.

It all leaves this investigation with far more questions than answers, and a lot more research ahead.

WAS IT WORTH IT?

In his glass-topped office building overlooking the Maria Magdalena church in Stockholm, Goran Stiernstedt, a doctor turned public health official, has spent many difficult hours going over what happened in his country during the swine flu pandemic, wondering if things should have been different.

“The big question is was it worth it? And retrospectively I have to say it was not,” he told Reuters in an interview.

Being a wealthy country, Sweden was at the front of the queue for pandemic vaccines. It got Pandemrix from GSK almost as soon as it was available, and a nationwide campaign got uptake of the vaccine to 59 percent, meaning around 5 million people got the shot.

Stiernstedt, director for health and social care at the Swedish Association of Local Authorities and Regions, helped coordinate the vaccination campaign across Sweden’s 21 regions.

The World Health Organization (WHO) says the 2009-2010 pandemic killed 18,500 people, although a study last year said that total might be up to 15 times higher.

While estimates vary, Stiernstedt says Sweden’s mass vaccination saved between 30 and 60 people from swine flu death. Yet since the pandemic ended, more than 200 cases of narcolepsy have been reported in Sweden.

With hindsight, this risk-benefit balance is unacceptable. “This is a medical tragedy,” he said. “Hundreds of young people have had their lives almost destroyed.”

PANDEMICS ARE EMERGENCIES

Yet the problem with risk-benefit analyses is that they often look radically different when the world is facing a pandemic with the potential to wipe out millions than they do when it has emerged relatively unscathed from one, like H1N1, which turned out to be much milder than first feared.

David Salisbury, the British government’s director of immunization, says “therein lies the risk, and the difficulty, of working in public health” when a viral emergency hits.

“In the event of a severe pandemic, the risk of death is far higher than the risk of narcolepsy,” he told Reuters. “If we spent longer developing and testing the vaccine on very large numbers of people and waited to see whether any of them developed narcolepsy, much of the population might be dead.”

Pandemrix was authorized by European drug regulators using a so-called “mock-up procedure” that allows a vaccine to be authorized ahead of a possible pandemic using another flu strain. In Pandemrix’s case, the substitute was H5N1 bird flu.

When the WHO declared a pandemic, GSK replaced the mock-up’s strain with the pandemic-causing H1N1 strain to form Pandemrix.

GSK says the final H1N1 version was tested in trials involving around 3,600 patients, including children, adolescents, adults and the elderly, before it was rolled out.

The ECDC’s Nicoll says early warning systems that give a more accurate analysis of a flu strain’s threat are the best way to minimize risks of this kind of tragedy happening in future.

Salisbury agrees, and says progress towards a universal flu vaccine – one that wouldn’t need last-minute changes made when a new strain emerged – would cuts risks further.

“Ideally, we would have a better vaccine that would work against all strains of influenza and we wouldn’t need to worry about this ever again,” he said. “But that’s a long way off.”

With scientists facing years of investigation and research, Emelie just wants to make the best of her life.

She reluctantly accepts that to do so, she needs a cocktail of drugs to try to control the narcolepsy symptoms. The stimulant Ritalin and the sleeping pill Sobril are prescribed for Emelie’s daytime sleepiness and night terrors. Then there’s Prozac to try to stabilize her and limit her cataplexies.

“That’s one of the things that makes me feel most uncomfortable,” she explains. “Before I got this condition I didn’t take any pills, and now I have to take lots – maybe for the rest of my life. It’s not good to take so many medicines, especially when you know they have side effects.”

(Reporting by Kate Kelland; Editing by Will Waterman)

http://news.yahoo.com/insight-evidence-grows-narcolepsy-gsk-swine-flu-shot-070212916–finance.html

 

Mount Sinai researchers discover how the flu virus tells time; Hides 8 hours in the Cell, then in 48 hours becomes infectious

Contact: Mount Sinai Press Office newsmedia@mssm.edu 212-241-9200 The Mount Sinai Hospital / Mount Sinai School of Medicine

Discovery provides new targets for antiviral drugs and vaccine designs

Scientists have discovered that that the flu virus can essentially tell time, thereby giving scientists the ability to reset the virus’ clock and combat it in more effective ways. According to researchers at the Icahn School of Medicine at Mount Sinai, the flu knows how much time it has to multiply, infect other cells, and spread to another human being. If it leaves a cell too soon, the virus is too weak. If it leaves too late, the immune system has time to kill the virus.

The finding provides a novel design platform for the flu vaccine and could lead to new antiviral drugs that make this viral clock dysfunctional. The research, led by Benjamin tenOever, PhD, Fishberg Professor of Microbiology at Mount Sinai, is published in the January 17th issue of Cell Reports.

With only ten major components, the virus needs to steal most of its resources from the human cell in order to multiply.  During this process, the virus often trips various “alarms” that equate to our immune system detecting, and then killing the virus. Dr. tenOever hypothesized that the virus must have a mechanism in place to keep track of how much time it has to steal these resources before the immune system springs into action. If the virus moves too fast, it will not have time to multiply. If it moves too slowly it will be stopped by the immune response. Dr. tenOever and his team wanted to find out how the virus knows exactly how much time it needs to multiply and move on.

“We knew that the virus has about eight hours in a cell to create enough copies of itself to continue spreading before the cell’s antiviral alarm would be set off,” said Dr. tenOever. “On a broader level, the virus needs two days of continuous activity to infect enough cells to permit spread to another human being. We wanted to tap into the flu’s internal clock and find a way to dismantle it to prevent the spread of the virus.”

Dr. tenOever and his team examined the processes that control the timing of infection. This research led to the discovery that, by relying on a quirk in our cell biology, the virus slowly accumulates one particular protein that it needs to exit the cell and subsequently spread to other cells, and eventually other humans—just in time before the immune system is activated.

Armed with this knowledge, Dr. tenOever and his team manipulated this timer by making the virus acquire this protein too fast, which caused flu to exit the cell too quickly and not have time to make more viruses. The next step was to manipulate the process to make flu acquire this protein too slowly, giving the immune system time to launch a response before the virus could escape, thereby killing the virus and preventing infection.  Dr. tenOever hopes this discovery will lead to new antiviral drugs that target the virus’s internal clock and that it will provide a new design platform for the flu vaccine. Currently, individuals have the option to receive a shot, which delivers dead virus through a needle, or a nasal spray, which contains live but weakened flu virus. Although the nasal spray vaccine is believed to be more effective than the shot, it is only FDA approved for individuals between the ages of 2-49. With data from the Cell Reports study, scientists will be able to develop a new type of spray vaccine that is composed of a virus with a “defective clock”.  This new option for protecting against flu may prove safer for the very old and very young who are unable to receive the current spray vaccine.

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This study was supported by the National Institutes of Health (grant numbers A1093571 and A1080624), Mount Sinai School of Medicine Mechanisms of Virus–Host Interactions T32 training grants, the Pew Charitable Trust, and the Burroughs Wellcome Fund.

About The Mount Sinai Medical Center

The Mount Sinai Medical Center encompasses both The Mount Sinai Hospital and Icahn School of Medicine at Mount Sinai. Established in 1968, the Icahn School of Medicine at Mount Sinai is one of the leading medical schools in the United States. The Icahn School of Medicine is noted for innovation in education, biomedical research, clinical care delivery, and local and global community service. It has more than 3,400 faculty members in 32 departments and 14 research institutes, and ranks among the top 20 medical schools both in National Institutes of Health (NIH) funding and by U.S. News & World Report.

The Mount Sinai Hospital, founded in 1852, is a 1,171-bed tertiary- and quaternary-care teaching facility and one of the nation’s oldest, largest and most-respected voluntary hospitals. In 2012, U.S. News & World Report ranked The Mount Sinai Hospital 14th on its elite Honor Roll of the nation’s top hospitals based on reputation, safety, and other patient-care factors. Mount Sinai is one of just 12 integrated academic medical centers whose medical school ranks among the top 20 in NIH funding and by U.S. News & World Report and whose hospital is on the U.S. News & World Report Honor Roll.  Nearly 60,000 people were treated at Mount Sinai as inpatients last year, and approximately 560,000 outpatient visits took place.

For more information, visit http://www.mountsinai.org/.

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Designer bacteria may lead to better vaccines: Contaminated vaccines work better!!!

Contact: Daniel Oppenheimer daniel.oppenheimer@utexas.edu 512-745-3353 University of Texas at Austin

Designer bacteria may lead to better vaccines

61 new strains of genetically engineered bacteria may improve the efficacy of vaccines for diseases such as flu, pertussis, cholera and HPV

AUSTIN, Texas — Researchers at The University of Texas at Austin have developed a menu of 61 new strains of genetically engineered bacteria that may improve the efficacy of vaccines for diseases such as flu, pertussis, cholera and HPV.

The strains of E. coli, which were described in a paper published this month in the journal PNAS, are part of a new class of biological “adjuvants” that is poised to transform vaccine design. Adjuvants are substances added to vaccines to boost the human immune response.

“For 70 years the only adjuvants being used were aluminum salts,” said Stephen Trent, associate professor of biology in the College of Natural Sciences. “They worked, but we didn’t fully understand why, and there were limitations. Then four years ago the first biological adjuvant was approved by the Food and Drug Administration. I think what we’re doing is a step forward from that. It’s going to allow us to design vaccines in a much more intentional way.”

Adjuvants were discovered in the early years of commercial vaccine production, when it was noticed that batches of vaccine that were accidentally contaminated often seemed to be more effective than those that were pure.

“They’re called the ‘dirty little secret’ of immunology,” said Trent. “If the vials were dirty, they elicited a better immune response.”

What researchers eventually realized was that they could produce a one-two punch by intentionally adding their own dirt (adjuvant) to the mix. The main ingredient of the vaccine, which was a killed or inactivated version of the bacteria or virus that the vaccine was meant to protect against, did what it was supposed to do. It “taught” the body’s immune system to recognize it and produce antibodies in response to it.

The adjuvant amplifies that response by triggering a more general alarm, which puts more agents of the immune system in circulation in the bloodstream, where they can then learn to recognize the key antigen. The result is an immune system more heavily armed to fight the virus or bacteria when it encounters it in the future.

For about 70 years the adjuvant of choice, in nearly every vaccine worldwide, was an aluminum salt. Then in 2009, the FDA approved a new vaccine for human papillomavirus (HPV). It included a new kind of adjuvant that’s a modified version of an endotoxin molecule.

These molecules, which can be dangerous, appear on the cell surface of a wide range of bacteria. As a result, humans have evolved over millions of years to detect and respond to them quickly. They trigger an immediate red alert.

“In some of its forms an endotoxin can kill you,” said Trent. “But the adjuvant, which is called MPL, is a very small, carefully modified piece of it, so it’s able to trigger the immune response without overdoing it.”

What Trent and his colleagues have done is expand on that basic premise. Rather than just work with an inert piece of endotoxin, they’ve engineered E. coli bacteria to express the endotoxin in many configurations on the cell surface.

“These 61 E. coli strains each have a different profile on their surface,” said Brittany Needham, a doctoral student in Trent’s lab and the first author on the paper. “In every case the surface structure of the endotoxin is safe, but it will interact with the immune system in a range of ways. Suddenly we have a huge potential menu of adjuvants to test out with different kinds of vaccines.”

One form might work better with cholera vaccine, another with pertussis (whooping cough) and another with a future HIV vaccine. Trent, Needham and their colleagues should be able to fine-tune the adjuvants with increasing precision as more E. coli strains are engineered and tested, and as their understanding of how they interact with the immune system deepens.

“I think we’re at the dawn of a new age of vaccine design,” said Trent. “For a long time vaccinology was really a trial-and-error field. It was a black box. We knew certain things worked. We knew certain vaccines had certain side effects. But we didn’t entirely know why. Now that’s changing.”

Trent said that an additional advantage of their system is that the E. coli can be engineered to express key viral and bacterial antigens along with the endotoxin. A single cell could deliver both parts of the one-two punch, or even a one-two-three punch, if antigens from multiple diseases were expressed in a single E. coli.

“It makes possible a vaccine that provides protection from multiple pathogens at the same time,” said Trent.

Trent and his colleagues are working on a second round of designer E. coli. They have also filed a provisional patent on their system and are working with the university to find a corporate partner to pay for clinical trials.

“This is ready to go,” said Trent. “I can’t predict whether it will actually make it to the market. But it’s very similar to the adjuvant that has already been approved, and my instinct is that if a company will undertake to do the trials, it will get approved. A company could call us tomorrow, we could send them a strain, and they could start working.”

FDA approves recombinant flu vaccine : Was rejected in 2009, arguing that there was insufficient evidence that the vaccine was safe

17 Jan 2013 | 19:49 GMT | Posted by Heidi Ledford |

The US Food and Drug Administration (FDA) has approved the first seasonal flu vaccine comprised of recombinant proteins, rather than inactivated or weakened virus.

The 16 January approval of Flublok, developed by Protein Sciences Corporation in Meriden, Connecticut, arrives as US emergency rooms are clogged with victims of an early and severe flu season. Thirty states are reporting high levels of flu-like illness this season, and New York state and the city of Boston have declared public health emergencies. Vaccine supplies are dwindling.

Flublok is one of a new wave of flu vaccines intended to make production more nimble. The three influenza hemagglutinin proteins comprising Flublok are made in insect cells rather than in chicken eggs, the classical incubator for seasonal flu vaccine. It is the second egg-free vaccine to be approved by the FDA. In November, the agency approved Flucelvax, made by the Swiss pharmaceutical firm Novartis.

But it has been a long road to approval for Protein Sciences. FDA advisors narrowly rejected the vaccine in 2009, arguing that there was insufficient evidence that the vaccine was safe. Development of Flublok and a related pandemic flu vaccine called Panblok was subsidized by a Biomedical Advanced Research and Development Authority (BARDA) contract awarded in 2009, but then threatened when Emergent BioSolutions of Rockville, Maryland and two other creditors sued Protein Sciences for failing to repay over $11 million in loans. The lawsuit was settled in 2010.

Flublok will be out on the market in full force in time for the 2013-2014 flu season, and limited supplies will be available to help out during the current season.

 

http://blogs.nature.com/news/2013/01/fda-approves-recombinant-flu-vaccine.html

Pigs in southern China infected with avian flu: Recent Infections of H1N1 & H3N2

Contact: Jim Sliwa jsliwa@asmusa.org 202-942-9297 American Society for Microbiology

Researchers report for the first time the seroprevalence of three strains of avian influenza viruses in pigs in southern China, but not the H5N1 avian influenza virus.  Their research, published online ahead of print in the Journal of Clinical Microbiology, has implications for efforts to protect the public health from pandemics.

Influenza A virus is responsible both for pandemics that have killed millions worldwide, and for the much less severe annual outbreaks of influenza. Because pigs can be infected with both human and avian influenza viruses, they are thought to serve as “mixing vessels” for genetic reassortment that could lead to pandemics, and pigs have been infected experimentally by all avian H1-H13 subtypes. But natural transmission of avian influenza to pigs has been documented only rarely.

In the study, from 2010-2012, Guihong Zhang and colleagues of the College of Veterinary Medicine, South China Agricultural University, Guangzhou, People’s Republic of China, tested 1080 21-25 week old pigs for H3, H4, H5, and H6 subtypes of avian influenza virus, and H1 and H3 subtypes of swine influenza virus. Thirty-five percent of the serum samples were positive for H1N1, and 19.7 percent were positive for H3N2 swine flu virus, and 0.93 percent, 1.6 percent, and 1.8 percent were positive, respectively, for the H3, H4, and H6 subtypes of avian influenza A virus. However, no serum samples collected in 2001 were positive for any of these viruses, indicating that transmission into swine was recent.

Given the recent transmission of avian influenzas into swine, “We recommend strongly that the pork industry worldwide should monitor the prevalence of influenza in pigs, considering their important role in transmitting this virus to humans,” says Zhang.

Previously, novel reassortant H2N3 influenza viruses were isolated from US pigs, which “were infectious and highly transmissible in swine and ferrets without prior adaptation,” according to a 2009 paper in the Journal of Molecular and Genetic Medicine by Wenjun Ma et al. Those viruses resembled, but were not identical to the H2N2 human pandemic virus of 1957.

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A copy of the manuscript can be found online at http://bit.ly/asmtip1212d.  Formal publication is scheduled for the February 2013 issue of the Journal of Clinical Microbiology.

(S. Su, W. Qi, J. Chen, W. Zhu, Z. Huang, J. Xie, and G. Zhang, 2012. Seroepidemiological evidence of avian influenza A virus transmission in pigs in southern China. J. Clin. Microbiol. Online ahead of print 21 November 2012.)

The Journal of Clinical Microbiology is a publication of the American Society for Microbiology (ASM).  The ASM is the largest single life science society, composed of over 39,000 scientists and health professionals. Its mission is to advance the microbiological sciences as a vehicle for understanding life processes and to apply and communicate this knowledge for the improvement of health and environmental and economic well-being worldwide.

Complete Genomics CEO rebuts warnings of national security risks / “a world in which a virus engineered to kill a specific individual can be ordered online for $500 “?

14 Dec 2012 | 20:53 GMT | Posted by Monya Baker |

In a letter to employees, sequencing company Complete Genomics CEO Cliff Reid predicts that the acquisition of his company by Chinese sequencing giant BGI will win approval by national security regulators and be completed by the end of March in 2013.

Back in September, the companies announced a $118-million dollar agreement under which Complete Genomics, which has a proprietary technology for sequencing human genomes, would become a BGI-owned subsidiary, with staff and facilities to remain in Mountain View, California. In a spurned counter-offer, San Diego, California-based Illumina presented itself as a better suitor to Complete Genomics, predicting that a deal with BGI would be blocked by part of the U.S. Treasury Department that oversees foreign investment in the U.S. (See Illumina, BGI spar over Complete Genomics)

Reid countered that Illumina’s proposal to acquire Complete Genomics would likely not get past antitrust regulators since Illumina dominates the sequencing market.

Reid’s letter came on the same day as an editorial in the San Jose Mercury News urging the committee on foreign investment to carefully scrutinize BGI’s acquisition of Complete Genomics for its impact on jobs and potential to advance bioweapons.

Reid noted in his letter that BGI already owns Illumina sequencing machines, and Illumina itself has a Chinese subsidiary selling directly to Chinese customers.

The editorial, by Michael Wessel and Larry Wortzel, two members of the U.S.-China Economic and Security Review Commission, a congressionally appointed advisory group, referred to a speculative scenario described in the Atlantic. It describes a world in which a virus engineered to kill a specific individual can be ordered online for $500. It goes on to note that North Korea, Pakistan, and Iran might all be willing to pay Chinese scientists from BGI for such projects.

The ability to design and synthesize a viral assassin would require technologies that go far, far beyond that required to sequence a human genome. Stanford synthetic biologist Drew Endy said the Atlantic article read like science fiction, at least for now. “I was shocked to see it published in that venue.”

Asked by Nature how worried he was that Complete Genomics’ technology could be used for bioweapons, Wessel said “The capabilities described in the Atlantic article might seem like science fiction, but so did the prospect of the Stuxnet-type virus just a couple of years ago.” (Stuxnet is a sophisticated computer worm that infected and disrupted machines used by Iran to refine uranium.)

The US-China Economic and Security Review Commission has taken no position on the transaction, Wessel said. “These concerns deserve to be strictly scrutinized by CFIUS [the Committee on Foreign Investment in the U.S.] to ensure that U.S. national security interests are protected.”

http://blogs.nature.com/news/2012/12/complete-genomics-ceo-rebuts-warnings-of-national-security-risks.html

Viruses cooperate or conquer to cause maximum destruction: They Change Behaviour to overcome our attempt to control them

Contact: Louise Vennells L.Vennells@exeter.ac.uk 44-013-927-22062 University of Exeter

Scientists have discovered new evidence about the evolution of viruses, in work that will change our understanding about the control of infectious diseases such as winter flu

Scientists have discovered new evidence about the evolution of viruses, in work that will change our understanding about the control of infectious diseases such as winter flu.

Researchers at the University of Exeter’s conducted experiments to manipulate a virus to see if it could evolve the ability to switch its behaviour according to how many other viruses infect a host.

Previous research has focussed on trying to force harmful microbes to become less threatening to human health as they evolve. But the new research, which was carried out in collaboration with the University of Oxford, proves viruses can readily develop the ability to adjust their behaviour to maximise their spread, in response to whether they are infecting as a single entity or in combination with other viruses.

Helen Leggett, a postgraduate researcher at the University of Exeter, was the lead scientist on the work, which is published online on December 13th in the journal Current Biology. She said: “Scientists are constantly searching for ways to limit the damage viruses can cause, to help reduce the impact of illnesses like winter flu and to respond to the next pandemic. Our work proves that regardless of how we try to manipulate viruses, they will always switch their behaviour to serve their own purposes and kill as many cells as possible. This study involved a relatively simple virus. If it can evolve so quickly, it’s reasonable to assume that a lot of other viruses and parasites can, too.”

The study was funded by the European Research Council, the Leverhulme Trust and the Natural Environment Research Council, while Helen Leggett is supported by the Biotechnology and Biological Sciences Research Council. The work also shed light on why organisms cooperate with each other. The virus would only cooperate with viruses which were related to it. When it infected alone it would clone itself within the cell, and would cooperate with those new viruses. In this context, cooperation meant killing the host relatively slowly so that the virus could replicate more.  But when it interacted with other viruses which were not related, it killed the cell faster, allowing it to out-replicate and dominate the other viruses.

Dosing schedule of pneumococcal vaccine linked with increased risk of getting multiresistant strain

 2010 study posted for filing

Contact: Elisabeth A. M. Sanders, M.D., Ph.D. l.sanders@umcutrecht.nl JAMA and Archives Journals

This release is also available in Chinese on EurekAlert! Chinese.

Infants who received heptavalent pneumococcal conjugate vaccination (PCV-7) at 2, 4, and 11 months were more likely than unvaccinated controls to have nasopharyngeal (in the nasal passages and upper part of the throat behind the nose) acquisition of pneumococcal serotype 19A, a leading cause of respiratory pneumococcal disease, according to a study in the September 8 issue of JAMA.

“A rapid increase in the presence of pneumococcal serotype 19A strains that are often multiresistant to antibiotics has been observed over the last decade. In the United States, serotype 19A is now the leading causative pneumococcal serotype of invasive and respiratory pneumococcal disease and the most frequently observed serotype in nasopharyngeal carriage. In the United States and other countries, the increase in serotype 19A disease was associated in time with the widespread implementation of PCV-7 in routine infant immunization programs,” according to background information in the article. “Because spontaneous fluctuations in time and antibiotic selective pressure may have induced this serotype 19A increase, controlled studies are needed to assess the role of PCV-7.”

Elske J. M. van Gils, M.D., of University Medical Center Utrecht, the Netherlands, and colleagues examined the association between PCV-7 vaccination and nasopharyngeal acquisition of serotype 19A pneumococci in 1,003 healthy newborns, with follow-up to the age of 24 months in the Netherlands, which has low antibiotic resistance rates. The study was conducted before widespread PCV-7 implementation in infants, between July 2005 and February 2008. Nasopharyngeal swabs were obtained at the age of 6 weeks and at 6, 12, 18, and 24 months. Infants were randomly assigned to receive 2 doses of PCV-7 at 2 and 4 months; 2 + 1 doses of PCV-7 at 2, 4, and 11 months; or no dosage (unvaccinated control group).

Nine hundred forty-eight children completed the study. Fifty-four nasopharyngeal serotype 19A carriage isolates from 318 in the 2-dose group, 66 isolates from 327 in the 2 + 1-dose group, and 33 isolates from 303 in the unvaccinated group were collected from 6 weeks through 24 months. “At 24 months and after having completed the vaccine series, the cumulative proportion of participants with acquisition of a new serotype 19A clone in the 2 +1-dose group was 16.2 percent (53 of 327) vs. 9.2 percent (28 of 303) in the unvaccinated control group. The cumulative proportion in the 2-dose group was also higher than in the unvaccinated group but did not reach statistical significance (13.2 percent; 42 of 318 children),” the authors write.

The proportion of children with new 19A acquisition who had used antibiotics in the last 6 months (18.7 percent) did not differ among groups.

“In addition to the contributing role of antibiotic selective pressure as previously described by others, we now have demonstrated, to our knowledge for the first time, the facilitating role of PCV-7 in nasopharyngeal acquisition of serotype 19A. In view of the proven disease potential of serotype 19A for otitis media and invasive pneumococcal disease and the observed association with antibiotic resistance, vaccines of broader coverage including protection against serotype 19A may further aid to pneumococcal disease prevention. However, we need to be aware that other serotypes with similar characteristics and disease potential may be the next in line to proliferate and therefore pneumococcal surveillance remains important after introduction of expanded pneumococcal conjugate vaccines,” the researchers conclude.

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(JAMA. 2010;304[10]:1099-1106. Available pre-embargo to the media at www.jamamedia.org)

Editor’s Note: Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

A vaccine-derived strain of poliovirus that has spread in recent years is serious but it can be tackled with an existing vaccine

2010 study posted for filing

Contact: Laura Gallagher l.gallagher@imperial.ac.uk 44-020-759-48432 Imperial College London

Polio research gives new insight into tackling vaccine-derived poliovirus

A vaccine-derived strain of poliovirus that has spread in recent years is serious but it can be tackled with an existing vaccine, according to a new study published today in the New England Journal of Medicine.

Vaccine-derived polioviruses can emerge on rare occasions in under-immunised populations, when the attenuated virus contained in a vaccine mutates and recombines with other viruses, to create a circulating vaccine-derived strain.

The researchers behind today’s study say their findings highlight the importance of completing polio eradication. They also say that should wild-type poliovirus be eradicated, routine vaccination with oral polio vaccines will need to cease, in order to prevent further vaccine-derived strains of the virus from emerging.

The study was carried out by researchers from the Medical Research Council Centre for Outbreak Analysis and Modelling at Imperial College London, working with the Government of Nigeria and the World Health Organization (WHO) research teams.

Poliovirus is highly infectious and primarily affects children under five years of age. Around one in 200 of the people infected with polio develop permanent paralysis, which can be fatal.

Polio was virtually wiped out by the early 2000s following a major vaccination drive by the Global Polio Eradication Initiative, but since then the number of cases of paralysis reported has plateaued, remaining roughly constant at between one and two thousand each year from 2003 to 2009, dropping only recently in 2010.

The first reported polio outbreak resulting from a circulating vaccine-derived poliovirus, known as a cVDPV, occurred in Hispaniola in 2000.  Prior to today’s study, there was little evidence available about the severity and potential impact of this kind of poliovirus.

Although billions of doses of oral vaccine have been distributed in the last decade, just 14 cVDPV outbreaks have been reported, affecting 15 countries. These outbreaks have usually been limited in size.

For the new study, researchers looked at the largest recorded outbreak of a cVDPV to date, which began to circulate in Nigeria in 2005. The authors examined data from 278 children paralysed by this cVDPV, and compared them with children paralysed by wild-type poliovirus in the country. Their analysis showed that this serotype 2 cVDPV is as easily transmitted and likely to cause severe disease as wild-type poliovirus of the same serotype.

The study also shows that vaccination with trivalent OPV, one of the main types of vaccine currently used to combat polio, is highly effective in preventing paralysis by this serotype 2 cVDPV.

The research shows that it is even more effective against cVDPV than against the wild-type polioviruses that are currently circulating, which can also be targeted with a different vaccine.

The new findings mean that it is particularly vital that efforts to vaccinate children with trivalent OPV continue in Nigeria and neighbouring countries, to protect children against all strains of polio. The scientists hope their findings will help countries to devise the right vaccine strategies to eradicate polio.

Helen Jenkins, the lead author of the study from the Medical Research Council Centre for Outbreak Analysis and Modelling at Imperial College London, said: “Our research shows that vaccine-derived polioviruses must be taken seriously and that we have the right tools to tackle them. We’ve had a lot of success against polio in the past and we’re optimistic that ultimately we should be able to eradicate it completely.

“However, our study shows that we can’t be complacent about the virus. It’s still vital for us to protect children from this dangerous and debilitating disease and we have to make sure we continue to vaccinate as many children as possible in affected countries for as long as wild-type poliovirus continues to circulate,” added Ms Jenkins.

Senior study author Dr Nicholas Grassly, also from the Medical Research Council Centre for Outbreak Analysis and Modelling at Imperial College London, added: “There has been some debate about the significance of circulating vaccine-derived polioviruses for the eradication initiative. Our research shows these viruses can be as pathogenic and transmissible as wild-type polioviruses and outbreaks must be responded to with just as much vigour.”

Dr Bruce Aylward, Director of the Global Polio Eradication Initiative at WHO, added:  “These new findings suggest that if cVDPVs are allowed to circulate for a long enough time, eventually they can regain a similar capacity to spread and paralyse as wild polioviruses.  This means that they should be subject to the same outbreak response measures as wild polioviruses.  These results also underscore the need to eventually stop all OPV use in routine immunization programmes after wild polioviruses have been eradicated, to ensure that all children are protected from all possible risks of polio in future.”

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This study was funded by the Medical Research Council and the Royal Society.

For further information please contact:

Laura Gallagher Research Media Relations Manager Imperial College London email: l.gallagher@imperial.ac.uk Tel: +44(0)20 7594 8432 Out of hours duty press officer: +44(0)7803 886 248

Notes to editors:

1. “Implications of a circulating vaccine-derived poliovirus (cVDPV) in Nigeria for polio eradication” New England Journal of Medicine, Wednesday 23 June 2010

Lead author: Helen Jenkins, Imperial College London (for full list of authors please see paper) Download a proof copy of the study (strictly embargoed) using this link:  https://fileexchange.imperial.ac.uk/files/3eba66aa7b6/Nigeria%20cVDPV%20paper%20R2%20clean.doc

2. About the Global Polio Eradication Initiative (GPEI)

The GPEI is spearheaded by national governments, WHO, Rotary International, the US Centers for Disease Control and Prevention (CDC) and UNICEF. Since 1988 (the year the GPEI was launched), the incidence of polio has been reduced by more than 99%. In 1988, more than 350,000 children were paralyzed each year in more than 125 endemic countries. In 2010, 349 cases have been reported and four countries remain endemic: Nigeria, India, Pakistan and Afghanistan.

Further information can be found at www.polioeradication.org. A list of countries in which there have been cases of polio reported since 2009 can be found at http://www.polioeradication.org/casecount.asp

3. About Imperial College London

Consistently rated amongst the world’s best universities, Imperial College London is a science-based institution with a reputation for excellence in teaching and research that attracts 14,000 students and 6,000 staff of the highest international quality. Innovative research at the College explores the interface between science, medicine, engineering and business, delivering practical solutions that improve quality of life and the environment – underpinned by a dynamic enterprise culture.

Since its foundation in 1907, Imperial’s contributions to society have included the discovery of penicillin, the development of holography and the foundations of fibre optics. This commitment to the application of research for the benefit of all continues today, with current focuses including interdisciplinary collaborations to improve global health, tackle climate change, develop sustainable sources of energy and address security challenges.

In 2007, Imperial College London and Imperial College Healthcare NHS Trust formed the UK’s first Academic Health Science Centre. This unique partnership aims to improve the quality of life of patients and populations by taking new discoveries and translating them into new therapies as quickly as possible.

Website: www.imperial.ac.uk

4. For almost 100 years the Medical Research Council has improved the health of people in the UK and around the world by supporting the highest quality science. The MRC invests in world-class scientists. It has produced 29 Nobel Prize winners and sustains a flourishing environment for internationally recognised research. The MRC focuses on making an impact and provides the financial muscle and scientific expertise behind medical breakthroughs, including one of the first antibiotics penicillin, the structure of DNA and the lethal link between smoking and cancer. Today MRC funded scientists tackle research into the major health challenges of the 21st century. www.mrc.ac.uk

Man’s best friend: Common canine virus may lead to new vaccines for deadly human diseases

Public Affairs News Service

Tuesday, Nov. 27, 2012

Writer: James  E.  Hataway, 706/542-5222, jhataway@uga.edu Contact: Biao He, 706/542-2855, bhe@uga.edu

Athens, Ga. – Researchers at the University of Georgia have discovered that a virus commonly found in dogs may serve as the foundation for the next great breakthrough in human vaccine development.

Although harmless in humans, parainfluenza virus 5, or PIV5, is thought to contribute to upper respiratory infections in dogs, and it is a common target for canine vaccines designed to prevent kennel cough. In a paper published recently in PLOS ONE, researchers describe how this virus could be used in humans to protect against diseases that have eluded vaccine efforts for decades.

“We can use this virus as a vector for all kinds of pathogens that are difficult to vaccinate against,” said Biao He, the study’s principal investigator and professor of infectious diseases in UGA’s College of Veterinary Medicine. “We have developed a very strong H5N1 flu vaccine with this technique, but we are also working on vaccines for HIV, tuberculosis and malaria.”

PIV5 does not cause disease in humans, as our immune system is able to recognize and destroy it. By placing antigens from other viruses or parasites inside PIV5, it effectively becomes a delivery vehicle that exposes the human immune system to important pathogens and allows it to create the antibodies that will protect against future infection.

This approach not only ensures full exposure to the vaccine but also is much safer because it does not require the use of attenuated, or weakened, pathogens. For example, an HIV vaccine delivered by PIV5 would contain only those parts of the HIV virus necessary to create immunity, making it impossible to contract the disease from the vaccine.

“Safety is always our number one concern,” said He, who is also a Georgia Research Alliance distinguished investigator and member of the Faculty of Infectious Diseases. “PIV5 makes it much easier to vaccinate without having to use live pathogens.”

Using viruses as a delivery mechanism for vaccines is not a new technique, but previous efforts have been fraught with difficulty. If humans or animals already possess a strong immunity to the virus used for delivery, the vaccine is unlikely to work, as it will be destroyed by the immune system too quickly.

“Pre-existing immunity to viruses is the main reason most of these vaccines fail,” He said.

But in this latest study, He and his colleagues demonstrate that immunity to PIV5 does not limit its effectiveness as a vaccine delivery mechanism, even though many animals-including humans- already carry antibodies against it.

In their experiments, the researchers found that a single dose inoculation using PIV5 protected mice from the influenza strain that causes seasonal flu. Another single dose experimental vaccine also protected mice from the highly pathogenic and deadly H5N1 virus commonly known as bird flu.

This recent work is a culmination of more than fifteen years of research and experimentation with the PIV5 virus, and He has confidence that it will serve as an excellent foundation for vaccines to treat diseases in both animals and humans.

“I believe we have the best H5N1 vaccine candidate in existence,” He said. “But we have also opened up a big field for a host of new vaccines.”

UGA Faculty of Infectious Diseases The University of Georgia Faculty of Infectious Diseases was created in 2007 to address existing and emerging infectious disease threats more effectively by integrating multidisciplinary research in animal, human and ecosystem health. Researchers from across the university focus on epidemiology, host-pathogen interactions, the evolution of infectious diseases, disease surveillance and predictors and the development of countermeasures such as vaccines, therapeutics and diagnostics. For more information about the Faculty of Infectious Diseases, see fid.ovpr.uga.edu.

UGA College of Veterinary Medicine The UGA College of Veterinary Medicine, founded in 1946, is dedicated to training future veterinarians, to conducting research related to animal and human diseases, and to providing veterinary services for animals and their owners. Research efforts are aimed at enhancing the quality of life for animals and people, improving the productivity of poultry and livestock, and preserving a healthy interface between wildlife and people in the environment they share. The college enrolls 102 students each fall out of more than 800 who apply.