Scientific Publications by FDA Staff

Emerg Infect Dis 2007 Mar;13(3):426-35

Matrix protein 2 vaccination and protection against influenza viruses, including subtype H5N1.

Tompkins SM, Zhao ZS, Lo CY, Misplon JA, Liu T, Ye Z, Hogan RJ, Wu Z, Benton KA, Tumpey TM, Epstein SL

Tompkins SM (reprint author), Univ Georgia, Dept Infect Dis, 111 Carlton St, Athens, GA 30602 USA Univ Georgia, Dept Infect Dis, Athens, GA 30602 USA Ctr Dis Control & Prevent, Atlanta, GA USA US FDA, Bethesda, MD 20014 USA

Changes in influenza viruses require regular reformulation of strain-specific influenza vaccines. Vaccines based on conserved antigens provide broader protection. Influenza matrix protein 2 (M2) is highly conserved across influenza A subtypes. To evaluate its efficacy as a vaccine candidate, we vaccinated mice with M2 peptide of a widely shared consensus sequence. This vaccination induced antibodies that cross-reacted with divergent M2 peptide from an H5N1 subtype. A DNA vaccine expressing full-length consensus-sequence M2 (M2-DNA) induced M2-specific antibody responses and protected against challenge with lethal influenza. Mice primed with M2-DNA and then boosted with recombinant adenovirus expressing M2 (M2-Ad) had enhanced antibody responses that crossreacted with human and avian M2 sequences and produced T-cell responses. This M2 prime-boost vaccination conferred broad protection against challenge with lethal influenza A, including an H5N1 strain. Vaccination with M2, with key sequences represented, may provide broad protection against influenza A.