Abstract
The successful isolation of a human influenza virus in 1933 was soon followed by the first attempts to develop an influenza vaccine. Nowadays, vaccination is still the most effective method to prevent human influenza disease. However, licensed influenza vaccines offer protection against antigenically matching viruses, and the composition of these vaccines needs to be updated nearly every year. Vaccines that target conserved epitopes of influenza viruses would in principle not require such updating and would probably have a considerable positive impact on global human health in case of a pandemic outbreak. The extracellular domain of Matrix 2 (M2e) protein is an evolutionarily conserved region in influenza A viruses and a promising epitope for designing a universal influenza vaccine. Here we review the seminal and recent studies that focused on M2e as a vaccine antigen. We address the mechanism of action and the clinical development of M2e-vaccines. Finally, we try to foresee how M2e-based vaccines could be implemented clinically in the future.
Highlights
Human influenza viruses are respiratory pathogens that are transmitted from an infected patient to another susceptible individual
It was found that the highly conserved M2 LC3-interacting region (LIR) close to the C-terminus of M2 bound to the LC3/ATG8 family members residing on autophagosome membrane, which mediated the redistribution of autophagosome on the plasma membrane of influenza A virus infected cells
We reported the presence of an major histocompatibility complex (MHC) class II restricted T cell epitope in M2e, that is restricted to BALB/c mouse strains (H-2d) and was strongly induced by mucosal vaccination by means of the recombinant protein CTA1-M2e-DD [64]
Summary
Human influenza viruses are respiratory pathogens that are transmitted from an infected patient to another susceptible individual. Not surprisingly, the conventional influenza vaccines that were ready to go in production in the spring of 2009, would have been close to futile to control the 2009 pandemic H1N1 outbreak [24] Such a profound antigenic change in HA (sometimes accompanied by a major change in NA subtype as well) compared with HA in previously circulating seasonal influenza viruses, is named an antigenic shift. As the epidemics of influenza A virus continue and the possible transmission of highly lethal avian influenza viruses from poultry to human remain a looming threat, vaccines that can induce broadly protective immune responses against influenza A are urgently needed Approaches to achieve this are based on the induction of cross-reactive antibodies or T cell responses against the more conserved internal viral proteins. Accessibility for antibodies and the relative ease with which anti-M2e immunogenicity can be elicited have led to numerous attempts and designs of M2e-based universal influenza A vaccines, a few of which have even been evaluated in early stage clinical trials
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