Researchers ferret out the truth about troubling H1N1 finding

During the 2009 outbreak of pandemic H1N1 influenza, Canadian researchers observed a troubling phenomenon: It appeared the new variant influenza caused more medically-attended illness if patients had been previously vaccinated against seasonal flu.Now those same researchers have confirmed their observation in the ferret model: Vaccination against seasonal flu worsened their acute symptoms when the animals were exposed to H1N1.“The ferret findings were consistent with our earlier human studies,” said Dr. Danuta Skowronski, the epidemiology lead for influenza and emerging respiratory pathogens at the BC Centre for Disease Control. “We used the best scientific methods—a double-blind, placebo-controlled animal study—and it shows that the observation was real,” she said at a media briefing at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy here.“We needed to follow up on those observational studies. They were clearly indicating something important about the interaction between seasonal and pandemic viruses.”She also illustrated her results in a late-breaking poster presentation.“Ferrets are an excellent model of human influenza disease,” Dr. Skowronski said, noting that performing a human study would have been unethical.The 16 ferrets vaccinated against seasonal influenza lost significantly more weight after H1N1 exposure than the 16 unvaccinated ferrets: 7.4% versus 5.2%. Lung virus titres were also significantly greater in the vaccinated ferrets: 4.96 plaque-forming units/ml versus 4.23 pfu/ml in the unvaccinated animals.Dr. Skowronski said the research community continues to mull the mechanism of action for the findings.“First, people attributed the human findings to bias and confounding. That is a common problem with observational studies,” she said. “Our ferret studies showed that the findings could not be explained away on the basis of confounding.“There may be a direct vaccine effect in which the seasonal vaccine induced some cross-reactive antibodies that recognized pandemic H1N1 virus, but those antibodies were at low levels and were not effective at neutralizing the virus” and may have actually facilitated its entry into cells.A second hypothesis is based on an indirect vaccine effect: By preventing infection with seasonal influenza, the vaccine may have denied recipients the beneficial cross-protection of such an infection against other viruses.When asked to comment, Dr. Laurent Kaiser, the chief of the Central Laboratory of Virology at the University Hospitals of Geneva, Switzerland, said: “Vaccination can change the face of disease, can prevent disease, and that’s the goal of vaccination. But we have to learn when it can change disease in ways we do not expect.”Dr. Kaiser did not participate in the animal studies.Dr. Skowronski said, “It is inevitable there will be another pandemic influenza virus outbreak. It is crucial that we understand what is that interplay, and how do these seasonal viruses interact with these novel viruses such as H5N1 and H7N1 and H3N2 that are out there. We have to learn what happened in 2009 in order to prepare for the next time.”She noted the current influenza vaccine includes protection against H1N1. MP

Researchers ferret out the truth about troubling H1N1 finding

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