Scientific Publications by FDA Staff

Vaccine 2008 Apr 16;26(17):2062-72

Comparison of vaccines for induction of heterosubtypic immunity to influenza A virus: Cold-adapted vaccine versus DNA prime-adenovirus boost strategies.

Lo CY, Wu Z, Misplon JA, Price GE, Pappas C, Kong WP, Tumpey TM, Epstein SL

Epstein, SL (reprint author), US FDA, Div Cellular & Gene Therapies, Off Cellular Tissue & Gene Therapies, CBER, 1401 Rockville Pike,HFM-730, Rockville, MD 20852 USA US FDA, Div Cellular & Gene Therapies, Off Cellular Tissue & Gene Therapies, CBER, Rockville, MD 20852 USA Ctr Dis Control & Prevent, Influenza Div, Natl Ctr Immunizat & Resp Dis, Cooodinating Ctr Infect Dis, Atlanta, GA 30333 USA NIAID, Vaccine Res Ctr, Bethesda, MD 20892 USA

Influenza epidemics or pandemics can arise for which strain- or subtype-matched vaccines are unavailable. Heterosubtypic immunity (Het-I) targeting conserved influenza A antigens could reduce morbidity and mortality during preparation of matched vaccines. Various vaccines inducing Het-I in animals have been studied separately using different viruses and conditions, but effectiveness for inducing Het-I has not been directly compared. The present studies compared immunization with cold-adapted (ca) viruses to DNA prime-recombinant adenovirus (rAd) boost vaccination to conserved antigens nucleoprotein (NP), matrix-2 (M2), or A/NP+M2. Both ca and DNA-rAd vaccinations induced antibody and T cell responses, and protected against lethal H1N1 challenge. Only A/NP+M2 DNA-rAd protected against challenge with highly pathogenic A/Vietnam/1203/2004 (H5N1); ca vaccine did not. Existing ca vaccines may provide some Het-I, but experimental vaccination focusing on conserved antigens was more effective in this model for protection against a divergent, highly pathogenic virus.