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?

Keywords: :

• antibody-dependent cytotoxicity
• heterosubtypic immunity
• Influenza A virus
• matrix protein 2
• protection mechanism
• recombinant protein
• vaccine

Acknowledgements

S Neirynck provided Figure 1A and M Huyghe produced Table 1.

Financial & competing interests disclosure

Research on influenza in the laboratory of W Fiers and X Saelens is supported by NIH grant 5R01AI055632, Instituut voor de Aanmoediging van Innovatie door Wetenschap en Technologie (IWT), Fonds voor Wetenschappelijk Onderzoek-Vlaanderen (FWO), Ghent University Bijzonder Onderzoeksfonds (BOF) and a research collaboration with Acambis Inc.

The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

The author thanks Walter Fiers and Amin Bredan for critical reading of the manuscript. No other writing assistance was utilized in the production of this manuscript.

Additional information

Funding

Research on influenza in the laboratory of W Fiers and X Saelens is supported by NIH grant 5R01AI055632, Instituut voor de Aanmoediging van Innovatie door Wetenschap en Technologie (IWT), Fonds voor Wetenschappelijk Onderzoek-Vlaanderen (FWO), Ghent University Bijzonder Onderzoeksfonds (BOF) and a research collaboration with Acambis Inc. The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. The author thanks Walter Fiers and Amin Bredan for critical reading of the manuscript. No other writing assistance was utilized in the production of this manuscript.