Influenza A viruses: why focusing on M2e-based universal vaccines

Abstract

The threat of highly virulent avian influenza, such as H5N1 and swine-origin H1N1 influenza viruses, bring out an urgent need to develop a universal influenza vaccine, which may provide cross-protection against different strain of influenza A viruses. The extra-domain of influenza M2 protein (M2e), which is almost completely conserved among all subtypes of influenza A viruses, is considered as a promising candidate target for the development of a broad-spectrum recombinant influenza A vaccine. The results of several preclinical studies with M2e protein, with or without carriers, have already proved the successful protection of M2e-based vaccinated animal model against lethal challenge of heterologous and homologous influenza A viruses. Recently, the results of Phase I/II clinical trail studies with M2e-based vaccines have raised hopes for considering these vaccines against seasonal and pandemic influenza A strains. Hence, it is expected that more and more effective and safe universal influenza vaccines based on M2e will be developed for prevention of seasonal and pandemic influenza in the near future.

Recombinant and epitope-based vaccines on the road to the market and implications for vaccine design and production

“…The ectodomain of the matrix protein 2 (termed M2e) is a potential target to design a universal influenza vaccine, as it consists of a 23 amino-acid peptide containing the B-cell linear epitope that is highly conserved across influenza virus subtypes. 17 Phase-I/II clinical trials with the M2e-peptide vaccine candidates have been successfully completed using a recombinant fusion protein (produced in E. coli) that links 4 tandem copies of the M2e peptide antigen to Salmonella Typhimurium flagellin and a TLR5 ligand (adjuvant). 18 The influenza virus HA stalk domain is also an attractive target for the induction of a cross-reactive humoral response, as it is more conserved than the head domain.…”

The Top Five “Game Changers” in Vaccinology: Toward Rational and Directed Vaccine Development

“…Variations of this approach have been used to integrate miRNA and mRNA expression levels (Cho et al, 2011), transcriptomic and proteomic datasets (Cheema et al, 2011), and lipidomic and transcriptomic data (Gupta et al, 2011). Excellent examples of the use of bioinformatics in vaccine design include: publicly available databases of user-supplied information merged with powerful analytical tools that allow investigators to explore systems level analysis of pertinent biological systems (Lynn et al, 2008;McGarvey et al, 2009), or the use of open reading frame, epitope prediction, and sequence conservation algorithms currently being used to develop broad-spectrum vaccines against Streptococcus (Maione et al, 2005) or Meningococcus B (Germain, 2010), as well as universal influenza vaccines (Ebrahimi and Tebianian, 2011).…”

High copy numbers and N terminal insertion position of influenza A M2E fused with hepatitis B core antigen enhanced immunogenicity

“…Passive immunization with these antibodies has reduced viral replication in the lungs of mice infected with influenza A virus (9). Therefore, the development of a universal influenza vaccine that can provide crossprotective effect against different subtypes has attracted considerable research interest (10)(11)(12). M2e is poorly immunogenic during natural infection (13).…”