A universal influenza A vaccine based on the extracellular domain of the M2 protein

The antigenic variation of influenza virus represents a major health proble m. However, the extracellular domain of the minor, virus-coded M2 protein i s nearly invariant in all influenza A strains. We genetically fused this M2 domain to the hepatitis B virus core (HBc) protein to create fusion gene c oding for M2HBc; this gene was efficiently expressed in Escherichia coli. I ntraperitoneal or intranasal administration of purified M2HBc particles to mice provided 90-100% protection against a lethal virus challenge. The prot ection was mediated by antibodies, as it was transferable by serum. The enh anced immunogenicity of the M2 extracellular domain exposed on HBc particle s allows broad-spectrum, long-lasting protection against influenza A infect ions.