Making the Case for H5N1 Influenza Research

The biologic properties that allowed mutated strains of avian H5N1 virus to pass between ferrets in a model of mammalian transmission all share certain, apparently critical biologic traits, Dr. Ron Fouchier said at an open meeting on H5N1 research held today and on April 4 in London.

“There is clearly a pattern of what biologic traits a virus needs to get” to allow mammalian transmission, an important clue to what to look for in naturally-occurring H5N1 mutations, said Dr. Fouchier, a researcher at Erasmus Medical Center in Rotterdam and head of one of the two groups that generated the controversial research papers that may now soon be published.

Along with the American Society for Microbiology, the UK’s Royal Society sponsored the two-day session that provided the most thorough information yet available on the H5N1 research done by Dr. Fouchier, and separately by Dr. Yoshihiro Kawaoka at the University of Wisconsin in Madison, as well as comments on the appropriateness of the research and its publication by several other speakers.

Dr. Kawaoka/image by Mitchel Zoler

Dr. Kawaoka described how he focused on the impact of mutations in the H5 hemagglutinin protein in viruses that combined the mutated gene with other genes from the 2009 pandemic H1N1 strain. He concluded from his work so far that “we need to enhance surveillance and the capacity to analyze H5N1 viruses and continue to identify mutations that would convert H5N1 viruses to those transmissible in mammals.” He also noted the “striking similarity” in findings between his work and that of Dr. Fouchier, even though they used different approaches for generating mammalian-transmissible forms of H5N1 (but both used ferret-model systems). Dr. Kawaoka also downplayed drawing a distinction between the mutations he generated and studied in his experiments and what might occur in the real world. “The risk is out there in nature” for the potential formation of H5N1 that is transmissible between mammals through the air. The four mutations he found that made airborne transmission possible between ferrets “is nothing” for a highly mutable virus like influenza.

Dr. Fouchier agreed. So far, spread of H5N1 virus from birds to mammals has been studied for 15 years. Air-borne spread of H5N1 between mammals will “eventually” happen he said; all it will take will be the passage of time, chance, and selection.

Dr. Fouchier/image by Mitchel Zoler

Dr. Fouchier noted that his experiments differed from Dr. Kawaoaka’s by not involving a reassortment step and dealing exclusively with the avian H5N1 virus. He said he was satisfied that the transmissible model strain he now has, which is not very efficiently passed between animals nor very pathogenic, was sufficient to move on to the next studies he wants to do: Look at the biologic traits of the transmissible virus and identify a set of key biologic properties that can be used for surveillance of naturally-occurring mutant strains; determine whether all H5N1 viral lineages have the potential to become transmissible between mammals; and determine whether any vaccine types seem best for pandemic preparedness.

Also speaking at today’s session was Dr. Thomas Inglesby, director of the Center for Biosecurity of the University of Pittsburgh, who reiterated his prior opinion that creating and studying engineered H5N1 mutants posed too big a health risk to proceed. He said that similar, valuable information could be obtained by studying naturally-occurring H5N1 mutations.

In his presentation, Dr. Paul Keim, acting chairman of the U.S. National Science Advisory Board for Biosecurity (NSABB), cited four reasons why the NSABB voted last week to recommend full publication of both Dr. Kawaoka’s and Dr. Fouchier’s papers on their research, reversing the position the Board first took last October. The revised versions of both articles that the NSABB examined last week had better clarity on the balance of risk and benefit from the research, and the Board also received additional, non-public information on benefits and risks, he said. The NSABB also drew on a new policy announced last week that set an official U.S. position on dual-use research, and the NSABB was also swayed by the lack of a mechanism for distributing restricted parts of the reports to approved recipients.

—Mitchel Zoler (on Twitter @mitchelzoler)


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Filed under Health Policy, IMNG, Infectious Diseases

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