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H5N1 Vaccine Stockpiling Concerns
Recombinomics Commentary 17:25
June 23, 2008
He also went on to add that they have extended this trial by re-immunizing some of the initial subjects. They took people from the first trial who had originally had 2 doses of the vaccine 21 days apart and gave them a booster 12-17 months later with a heterologous virus. This booster showed that the immune system had been well primed by the initial series and in 7 days gave good antibody titres to both the new and original virus. This data is supportive of using a prepandemic vaccine followed by a true pandemic vaccine.
The above comments are from a synopsis of a talk given at the 13th International Conference on Infectious Disease in Kuala Lampur, Malaysia by Gregory Berezuk of Baxter BioScience.
The original Baxter vaccine was grown in vero (African green monkey) cells and used a clade 1 isolate as the target. The published data indicated the initial response was weak and data was presented on patients with a titer of 20 or higher. However, the above comments suggest that a follow-up booster produced “good” antibody titers in 7 days against the original target as well as the heterologous (presumably clade 2) booster.
These data, coupled with reports on the time to produce a vaccine target, suggest that the current approved vaccines should be used to prime populations, rather than be stockpiled for use after the pandemic begins, which is the current plan for many countries.
Recently Japan, like other countries with active H5N1 infections and prior human infections, has announced plans to begin vaccinations of first responders, as well as a broader population, in the upcoming months, in advance of an H5N1 outbreak. This approach is supported by the above results, and provides a number of advantages over stockpiling.
Most of the current stockpiled vaccines are directed against clade 1 targets from 2004 patients in Vietnam. Although clade 1 is still in circulation in birds in southeast Asia, most of the human infections there are clade 2 (Fujian clade 2.3.4), which is also true for human infections in China. The recent reports of clade 2.3 in long range migratory birds in Japan, with related sequences in South Korea and southeastern Russia, may have contributed to Japan’s decision to accelerate its vaccination implementation plan, which is likely to target clade 2. Last year the H5N1 in Japan and South Korea was clade 2.2.2 (subclade of Qinghai strain).
Although the current set of targets may not be exact matches of circulating H5N1, the virus is not established in human populations, so the use of these vaccines is unlikely to accelerate H5N1 evolution. In contrast, stockpiling vaccine and subsequent use after a pandemic begins is likely to accelerate H5N1 evolution, which will impact subsequent vaccines, which will require approximately 6 month to create and distribute. Trailing a rapidly evolving H5N1 by six months would limit the effectiveness of the pandemic vaccine.
Thus, stockpiling vaccines for use by first responders may have significant downside for the general population, which could be overcome by starting vaccinations now, to prime a broad population for future booster shots.
Recombinomics Paper at Nature Precedings