Abstract � Fiscal Year 2003

Abstract: Influenza continues to pose a serious public health problem. The threat is worse if an unexpected strain or even new pandemic subtype of influenza virus emerges, to which people are not immune. With no way to know when a pandemic might occur or how much lead time we would have to develop strain-matched vaccines, additional approaches to vaccination should be explored.

Heterosubtypic immunity against conserved influenza A virus components has long been studied in animals. It confers broad protection against a wide range of strains of varied subtypes, and thus its use does not require prediction of viral strains that will circulate. We have previously shown that DNA vaccination using genes for conserved influenza virus antigens NP and M can protect against heterosubtypic challenge viruses, including some strains of the potential pandemic subtype H5N1. Vaccination with conserved influenza antigens could provide a first line of defense in the early stages of a pandemic, before antigenically matched vaccines were available.

In order to improve induction of broad cross-protection, we propose immunization with a variety of DNA prime-viral boost regimens. Antibody and T cell responses will be measured, and protective immunity assessed by challenge with heterosubtypic influenza viruses. The prime-boost regimens identified as most effective will be tested against challenge with viruses of potential pandemic subtypes. Results will advance our knowledge about modes of protection against new pandemic viruses that could be used routinely in advance, rather than waiting to identify a strain and manufacture a matched vaccine.

Institution: Food and Drug Administration

Date: July 2003

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Last updated: July 16, 2003

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