M2 protein is a single-pass type III membrane protein forming homotetramers representing pH-gated proton channel incorporated into the viral lipid envelope. This proton channel is essential for efficient release of viral genome during viral entry [32]. M2 protein is abundantly expressed at the apical plasma membrane of infected epithelial cells, but only a small number (16-20 molecules/virion) of M2 molecules are incorporated into virions [33, 34] . Great attention is paid to the extracellular N-terminal domain of M2 protein (eM2), a 23 amino acid peptide, which is highly conserved in all human influenza A strains. It is therefore an attractive target for preparation of a universal influenza A vaccine. In contrast to hemagglutinin and neuraminidase, eM2 is a weak immunogen [35] . Therefore, various approaches to increase its immunogenicity were used. All of them are based on increasing the immunogenicity of small antigen molecules by insertion of their multiple copies into a suitable immunogen Neirynck et al [36] prepared a fusion protein composed of eM2 and hepatitis B virus core (HBc) protein. This fusion protein has the ability to aggregate into the highly immunogenic virus-like particles inducing a long-lasting protection against lethal influenza A infection. High in vivo protective effect of described virus-like particles was proven after intraperitoneal or intranasal immunization of mice and subsequent infection with lethal dose of influenza viruses of various HA subtypes [37] . Efficacy of these particles has been increased by application of new adjuvant CTA1-DD. Combination of the eM2-HBc construct with the new adjuvant led to the protection of mice against lethal infection and a remarkably lower morbidity [38] . Various constructs of eM2 peptide engineered by conjugation to carrier proteins were evaluated as a vaccine, which successfully protected animals against infection with homologous but also heterologous human strains [24,36,37,39-42].