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H5N1 Bird Flu Evolution and Spread Outpace Pandemic Vaccine

Recombinomics Commentary

August 7, 2005

Medical experts in Asia, where all of the human and poultry cases of bird flu have occurred, cautioned on Sunday that formidable obstacles remained before the new vaccine would become a useful tool in preventing a pandemic.

The biggest impediment may be the rapid evolution of the virus itself.

Dr. Guan Yi, a Hong Kong University microbiologist, said that the flu virus that has just appeared this summer among migratory birds roosting on an island in Qinghai Lake in western China had quite a few genetic differences from previous viruses that had circulated in Southeast Asia.

The previous viruses appear to have been used in the successful vaccine tests this spring and summer in the United States.

"It keeps changing, it keeps evolving," he said. "We don't know how much the vaccine matches."

The above comments confirm the concerns about the ability of the pandemic vaccine that is being developed worldwide to have utility against the H5N1 that has emerged from Qinghai Lake and is now rapidly spreading across southern Russia and northern Kazakhstan.

This version of H5N1 is considerably different than the H5N1 in Vietnam and the current vaccine is unlikely to have significant activity.  The new vaccine requires at least 2 injections of 90 micrograms.  The 180 micrograms is 12 times higher then the amount used for a human flu isolate.  Moreover, the dose response is border-line, so a third injection may be required.  Thus, almost 20 times the normal dose may be necessary, and the H5N1 has a tendency to kill the chicken eggs, reducing the yield.  Thus, the availability of chicken eggs could severely limit the amount of vaccine produced and could conceivable require 50 times the number of eggs required to make a vaccine against one human isolates (the current human trivalent vaccine is made against three viruses using 15 micrograms each).

These data suggest that the vaccine under development may not work well against the 2005 H5N1 in Vietnam, which only has 4 amino acids changes in HA, because the vaccine against the immunizing isolate is so weak. 

As H5N1 closes in on Europe and threatens to spread throughout Asia and beyond, it is clearly time to rethink and retool vaccine development, which uses technology developed shortly after the first human flu virus was isolated in 1933.  The techniques used in 2005 are strikingly similar to the technology of the 1940's, and the case fatality rate of the 2005 H5N1 is 10 to 20 times higher than the 1918 pandemic virus.

Although efficient human-to-human H5N1 transmission has not been confirmed, the rapid evolution of H5N1 and its increased host and geographical range, creates a very unstable genetic situation.

This instability could have dire consequences in the very near term.

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