The Influenza Matrix Protein 2 as a Vaccine Target

Abstract

Matrix protein (M)2 is an Influenza A, type III membrane protein with an extracellular domain (ectodomain of M2 [M2e]) of 23 amino acid residues, which is strongly conserved across virus strains. M2 fulfills an important biological function in the life cycle of the Influenza A virus and has been a target of antiviral drugs. M2e has generated much interest as a potential vaccine target, and a clinical M2e vaccine trial was initiated in 2007. The advantage of M2e compared with hemagglutinin, the prime antigen target in conventional influenza vaccines, is that its sequence is conserved. This means that a stable, efficacious and easily produced M2e-based vaccine would provide protection not only against drifting seasonal influenza epidemic strains, but would also make it possible to vaccinate in anticipation of an emerging pandemic. Furthermore, most reported M2e-based vaccines are produced by economical and safe technologies. IgG subtype antibodies directed against M2e can prevent death from influenza and reduce morbidity in animal models for influenza disease. The immunological mechanism that mediates protection by anti-M2e antibodies is not completely understood, but it probably involves antibody-mediated cellular cytotoxicity. This review summarizes the findings on M2e vaccine candidates and addresses some of the key unanswered questions about this promising Influenza A vaccine target: what is its likely mechanism of action? Which measurable parameters correlate with protection? And what can be expected from clinical use of an M2e-based vaccine?

Genome packaging in influenza A virus

“…For instance, it has been suggested that packaging signals are good targets for oligonucleotide-based inhibition (Giannecchini et al, 2009). In a similar vein, the M2 ectodomain has been proposed as a candidate immunogen for a 'universal' influenza vaccine, for which antigenic escape mutants will be less likely to develop because the M2e coding region is either congruent with or overlaps that of M1 (Saelens, 2008). We speculate that the fact that the first nine codons of the M2e coding region also overlap the segment 7 packaging signal (Gog et al, 2007;Hutchinson et al, 2008;Ozawa et al, 2009) will further constrain the development of escape mutants.…”

Application of an immunoglobulin Y-alkaline phosphatase bioconjugate as a diagnostic tool for influenza A virus

“…Furthermore, M2e is highly expressed on infected cell surfaces and exhibits antigenic properties. Therefore, M2e-specific antibodies can bind to cells infected by the virus [19] . For this reason, the M2e peptide is considered to be an excellent tool for the diagnosis of influenza A virus [6].…”