M2 protein in its native state forms a homotetramer, comprising also conformational epitopes, which might play important role in eM2 immunogenicity. It was shown that oligomer-specific antibodies were induced by recombinant eM2 protein mimicking the natural quaternary structure of M2 ectodomain in viral particle [43] . For this purpose, a modified version of leucine zipper from yeast transcription factor GCN4 was bound to eM2. High titers of antibodies recognizing M2 protein in the native conformation were obtained after intraperitoneal or intranasal immunization with this recombinant protein, and immunized mice were fully protected against lethal dose of influenza A virus [43] . Such vaccine could improve quality of humoral immune response with antibodies elicited not only against linear epitopes but also against conformational epitopes.