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Avian Influenza Update, January 20, 2006

By Luciana L. Borio, M.D., January 20, 2006

Turkey

On January 18, the WHO reported that laboratory tests have confirmed H5N1 infection of a 4 year old Turkish boy, which brings the total number of human cases in Turkey to 21, with 4 deaths. A WHO collaborating laboratory in the U.K. is processing additional specimens from Turkey for diagnostic confirmation and to determine whether there are additional cases. The lab is also undertaking viral characterization to assess viral evolution and conducting antigenic analyses to determine the optimal course for continued pandemic vaccine development.

Evolution of the H5N1 Virus

To date, three mutations in the virus’s sequence have been identified (Butler D. Alarms ring over bird flu mutations. Nature 2006;439:248-249). At least two of them may make the virus better adapted for infecting humans. The first mutation involves the hemagglutinin receptor protein, which allows the virus to bind to receptors on the surface of its host’s cells and increases the virus’s ability to bind to human receptors and infect humans. The second mutation reported by WHO involves a substitution of glutamic acid with lycine at position 627 of the polymerase protein, which allows the virus to replicate. According to the report in Nature, glutamic acid is associated with viral replication in birds, whereas lycine is associated with replication in primates. It is suspected that these two mutations may also facilitate human-to-human transmission of the H5N1 virus.

Disappointing Vaccine Trials

NIAID clinical trials of an H5N1 pandemic vaccine candidate have proven disappointing. The vaccine tested was substantially less immunogenic than interpandemic influenza vaccine and reportedly required two doses, each containing 90 micrograms of antigen, to elicit a satisfactory immune response. The NIAID is currently investigating other strategies, such as alternative routes of administration and the use of adjuvants to enhance immunogenicity. They are even considering pre-emptive vaccination to prime the population for an antibody response to a novel virus (Subbarao K, et al. Development of effective vaccines against pandemic influenza. Immunity 2006;24:5-9). These strategies likely assume that a pandemic will not occur for at least a couple of years. However, if this virus continues to adapt to humans as rapidly as it appears to be doing in Turkey, it is unlikely that sufficient vaccine will be available to avert a pandemic.