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 fulllength 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.

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We have investigated the role of MHC class I products and CD8 T cells in regulating Ab responses using β2-microglobulin deficient (β2m−/−) mice. β2m−/− mice produced stronger IgM and IgG responses than did control β2m+/+ mice to both cellular and viral Ags. These Ab responses could be suppressed by infusion of activated B cells from β2m+/+ mice. Further investigation showed that the β2m-associated molecule on activated B cells that induced CD8 suppression was Qa-1 and that the Th2 component of CD4 cells was most affected by CD8-suppressive activity. Our findings suggest a novel pathway of Th inhibition in which B cell presentation of Qa-1-associated peptides stimulates CD8 suppressive activity.