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:


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



Aspirin, Tylenol May Decrease Effectiveness of Vaccines: “if you block COX-1, you might be decreasing the amount of antibodies your body is producing”

2009 study posted for filing

Contact: Kelsey Jackson JacksonKN@missouri.edu 573-882-8353 University of Missouri-Columbia

Aspirin, tylenol may decrease effectiveness of vaccines

Mizzou scientists discover aspirin and Tylenol block enzymes that could inhibit vaccines

COLUMBIA, Mo. – With flu season in full swing and the threat of H1N1 looming, demand for vaccines is at an all-time high. Although those vaccines are expected to be effective, University of Missouri researchers have found further evidence that some over-the-counter drugs, such as aspirin and Tylenol, that inhibit certain enzymes could impact the effectiveness of vaccines.

“If you’re taking aspirin regularly, which many people do for cardiovascular treatment, or acetaminophen (Tylenol) for pain and fever and get a flu shot, there is a good chance that you won’t have a good antibody response,” said Charles Brown, associate professor of veterinary pathobiology in the MU College of Veterinary Medicine. “These drugs block the enzyme COX-1, which works in tissues throughout the body. We have found that if you block COX-1, you might be decreasing the amount of antibodies your body is producing, and you need high amounts of antibodies to be protected.”

COX enzymes play important roles in the regulation of the immune system. The role of these enzymes is not yet understood completely, and medications that inhibit them may have adverse side effects. Recent research has discovered that drugs that inhibit COX enzymes, such as COX-2, have an impact on the effectiveness of vaccines. Brown’s research indicates that inhibiting COX-1, which is present in tissues throughout the body, such as the brain or kidneys, could also impact vaccines’ effectiveness.

These MU researchers also are studying the regulation of inflammation and how that leads to the development or prevention of disease. Many diseases, such as arthritis, cardiovascular disease and diabetes, are all chronic inflammatory diseases. Contrary to previous beliefs, inflammation is generally a good thing that helps protect individuals from infection. Many of the non-steroidal drugs that treat inflammatory conditions reduce antibody responses, which are necessary for treating infections.

“So far, we’ve tested this on an animal model and have found that these non-steroidal drugs do inhibit vaccines, but the next step is to test it on humans,” Brown said. “If our results show that COX-1 inhibitors affect vaccines, the takeaway might be to not take drugs, such as aspirin, Tylenol and ibuprofen, for a couple weeks before and after you get a vaccine.”


Brown’s research, “Cycloozygenase-1 Orchestrates Germinal Center Formation and Antibody Class-Switch via Regulation of IL-17,” has been published in The Journal of Immunology.