Immunization with high epitope density of M2e derived from 2009 pandemic H1N1 elicits protective immunity in mice

As highly conserved amongst human influenza A strains, the extracellular domain of influenza M2 protein (M2e) is considered and proved as a promising candidate for a universal influenza vaccine. However, there are four amino acid variations in the M2e sequence of the 2009 pandemic H1N1 (referred to as "swine flu M2e, SFM2e") compared with the conventional M2e consensus sequence. Whether the sequence variation alters the immunogenicity and protection of SFM2e epitope remains unclear. In our present study, we synthesized SFM2e peptide and constructed a series of GST fusion proteins containing various copies of the SFM2e epitope and immunized mice to evaluate their immunogenicity and protective activity. We found that although the amino acid variations have weakened the immunogenicity of the SFM2e peptide, the SFM2e fusion proteins with high epitope densities induced intense and diverse antibody response as well as T cell response. Moreover, mice immunized with high epitope density of SFM2e were nearly fully protected against a lethal challenge by the mouse-adapted influenza virus A/Porto Rico/8/34. Our study could provide new available data to improve the epitope vaccine strategy against influenza pandemic.