This finding, coupled with results of previous studies that showed protection against multiple human influenza strains, suggests that such a vaccine would protect humans against multiple variants of the bird and human influenza viruses, according to Richard Webby, Ph.D., assistant member of Infectious Diseases at St. Jude. Such a vaccine could protect humans against an H5N1 "bird flu" virus that mutates so that it adapts to humans and can readily spread from person to person, Webby said. Flu experts and public health officials fear that such an H5N1 variant would trigger a human pandemic (worldwide epidemic).
Webby is scheduled to present the findings of this study at the U.S. Public Health Service Professional Conference in Denver, Colo., May 3 at 12:30 pm EDT.
The investigators used two versions of Vical’s multi-component, DNA-based vaccine in the studies. One vaccine was directed against three viral proteins: NP and M2, which are "conserved" proteins that generally do not mutate quickly and therefore, are slow to avoid immune responses triggered by the vaccine; and H5, a "variable" protein on the surface of the bird and human flu viruses that is critical to their ability to infect cells. This variable protein is known to mutate readily, thereby foiling previous immune responses it triggered--whether due to natural exposure or vaccination. The other version of the vaccine contained only the two conserved viral proteins.
In the St. Jude study, the full, three-component vaccine (H5, NP and M2) provided complete protection in mice against lethal challenges with a highly virulent (Vietnam/1203/2004) H5N1 avian influenza virus. Moreover, other studies showed that a smaller version of the vaccine containing only the NP and M2 components provided significant protection against several strains of human influenza virus as well as the H5N1 "bird flu" strain.
"Such cross-protection against bird and human influenza is considered by researchers to be the ’Holy Grail’ of flu vaccines," Webby said. "By stimulating immune responses against targets not likely to mutate, the vaccine could trigger an immune defense against a broad range of variants of the virus.
"Even if the bird flu virus mutates so it becomes adapted to humans, this kind of cross protection will allow the immune system to track and attack such an emerging new variant without missing a beat," Webby said. "We wouldn’t have to wait to start developing a vaccine against it until after the original virus mutated."
Webby’s team showed that all mice and ferrets that received the DNA vaccine survived the challenge with the virulent H5N1 strain, while those that received a "blank" vaccine control did not survive. The vaccine also prevented weight loss in all animals challenged with the virulent virus, suggesting that the vaccine might also protect humans against serious flu-related sickness.
The studies included 16 mice or six ferrets in each vaccine or control group. The DNA vaccines targeted NP and M2--with and without the H5 avian influenza virus surface protein. All test DNA vaccines were formulated with the company’s VaxfectinTM adjuvant. An adjuvant is an additive administered with a vaccine that has little effect by itself, but improves the response of the immune system to the vaccine.
Carrie Strehlau | EurekAlert!
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