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

 

A small genetic change makes flu virus deadly ( H5N1 2001 Requested Repost)

Contact: Jeff Minerd jminerd@niaid.nih.gov 301-402-1663 NIH/National Institute of Allergy and Infectious Diseases

A small genetic change makes flu virus deadly

A tiny change in one of the influenza virus’s 10 genes is key to making certain strains of the virus especially virulent to humans, scientists report in the Sept. 7 issue of Science. This discovery helps explain why an influenza outbreak four years ago in Hong Kong killed an unusually high proportion of the people it infected – six out of 18, says lead researcher Yoshihiro Kawaoka, D.V.M., Ph.D., of the University of Wisconsin-Madison.

“We have found that a limited number of very tiny genetic changes in a specific gene, one called PB2, can have a big effect on how potent the influenza virus is,” says Dr. Kawaoka, a grantee of the National Institute of Allergy and Infectious Diseases (NIAID).  “Because the influenza virus constantly mutates, and because only a few changes can make a non-pathogenic virus highly pathogenic, we should assume that an outbreak of any new strain or subtype is potentially dangerous to humans.”

“To prepare for future influenza pandemics, NIAID has supported efforts to understand how new virus strains potentially harmful to humans appear,” says Anthony S. Fauci, M.D., NIAID director. “This study is an elegant example of research that provides insight into the emergence of virulent viruses and can help us develop better strategies for detecting future outbreaks.”

Wild waterfowl are natural reservoirs for the influenza virus; these birds transmit the virus to pigs or chickens, which then pass it on to people. The deadly outbreak of influenza virus subtype H5N1 in Hong Kong in 1997 was the first documented case of an influenza virus jumping directly from chickens to people.  Public health authorities responded by ordering the slaughter of more than 1 million live poultry to prevent further spread of the virus to humans.

Dr. Kawaoka and colleagues obtained samples of the H5N1 viruses that had infected Hong Kong residents during the 1997 outbreak. Testing these viruses in laboratory mice, the researchers found good correlation between how sick certain H5N1 strains made mice and how sick they had made humans.  The researchers divided the H5N1 strains into two groups: one that caused systemic lethal infection in the mice and one that was relatively benign.  Mice are a good model for studying H5N1, Dr. Kawaoka says, because this virus affects mice and humans similarly.

Next, Dr. Kawaoka used a technology that allows him to genetically engineer “designer” influenza viruses from scratch.  By systematically swapping the genes from the harmful and benign viruses, then testing how those engineered viruses affected mice, he discovered that the PB2 gene from the harmful group gives the virus its potency.  Then, through testing viruses that contained variations of this PB2 gene, he further identified a tiny change within the gene – a change of just one unit of RNA – that appears to be key to the virus’s virulence.

The function of the PB2 gene is not completely understood, but scientists believe it codes for an enzyme that helps force the host cell’s molecular machinery to make more viruses, Dr. Kawaoka explains.  “We don’t know if the mutation we studied is involved in that process, but our next step will be to find out,” he says.

Just over 10 years ago, researchers developed the ability to genetically engineer influenza viruses, a process known as reverse genetics.  In 1999, Dr. Kawaoka, with support from NIAID, streamlined this technology, making it much more efficient.  Without the ability to engineer influenza viruses through the reverse genetics system, it would not have been possible to create and study variations of the H5N1 virus, Dr. Kawaoka says.  “Just a few years ago, this discovery would not have been possible,” says Carole Heilman, Ph.D., director of NIAID’s Division of Microbiology and Infectious Diseases. “We believe this is the first of many more important discoveries that will arise from this technology.”

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For more information on Dr. Kawaoka’s work in this field, other NIAID-supported influenza research, and background on the virus itself, visit Focus on the Flu on the NIAID Web site at http://www.niaid.nih.gov/newsroom/focuson/flu00.  Focus on the Flu also contains information on NIAID-sponsored efforts to prepare for future influenza pandemics.  Such efforts include helping to fund ongoing monitoring of influenza virus strains circulating through live poultry markets in Hong Kong, a project that could nip future outbreaks in the bud.  Other NIAID-supported researchers are examining the history of influenza virus evolution for clues about which new strains might emerge next.

NIAID is a component of the National Institutes of Health (NIH).  NIAID supports basic and applied research to prevent, diagnose, and treat infectious and immune-mediated illnesses, including HIV/AIDS and other sexually transmitted diseases, tuberculosis, malaria, autoimmune disorders, asthma and allergies.

Reference:

Hatta M et al.  Molecular basis for high virulence of Hong Kong H5N1 influenza A viruses.  Science 293(5536):1840-42 (2001).

Press releases, fact sheets and other NIAID-related materials are available on the NIAID Web site at http://www.niaid.nih.gov.