Characterizations of four monoclonal antibodies against M2 protein ectodomain of influenza A virus

M2 protein of influenza A virus has been implicated as a target for vaccines with broad cross-strain coverage. Studies in small animal models have shown that antibody responses induced by 23-mer M2 peptide vaccines can provide protection against influenza A virus challenge. To study antiviral mechanisms of Merck M2-OMPC conjugate vaccine, we generated and characterized four M2 peptide-specific monoclonal antibodies (mAbs). Here we demonstrated that the protection by our M2 mAbs is independent of NK-mediated effector functions in mice. The protective mAbs preferentially bind to M2 multimers composed of two or more M2 peptides in parallel orientation. Our findings indicate that the protective M2 Ab prefer to bind to epitopes located within the N-terminal 10 amino acids of the M2 peptide, and the epitopes are likely formed by two M2 peptides in parallel orientation. The implications of these results in antiviral mechanisms of immune responses induced by M2 vaccines are discussed.