The 23-residue external domain of the influenza A virus M2 protein (M2e) has significant potential as a vaccine antigen. Here, we describe the construction and characterization of an M2e-modified Sindbis virus designated E2S1-M2e. E2S1-M2e virions contain M2e as an N-terminal extension of the E2 glycoprotein and therefore express 240 copies of the M2e peptide on their surface. The E2S1-M2e virus expressed M2e in an accessible and immunogenic form and induced M2e-specific antibodies when administered to mice. Mice that received an intranasal vaccination with E2S1-M2e were protected against a lethal challenge with a virulent, mouse-adapted strain of influenza A virus.
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