tetano
Editor, Senior Moderator
J Infect Dis. 2019 Jan 31. doi: 10.1093/infdis/jiz003. [Epub ahead of print]
[h=1]The Role of M2e in the Development of Universal Influenza Vaccines.[/h] Saelens X[SUP]1,[/SUP][SUP]2,[/SUP][SUP]3[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Two decades ago, the influenza A virus matrix protein 2 ectodomain (M2e) was proposed as a universal influenza A vaccine candidate. Today it still is. M2e is very conserved, poorly immunogenic in the context of natural infections, and can be rendered highly immunogenic by fusing it to almost any carrier that is suitable for use as a vaccine. Numerous studies in laboratory mice, but very few in natural influenza A virus hosts, have demonstrated that M2e-based vaccines can provide protection against any influenza A virus challenge. The production of M2e vaccines is feasible in economic and safe microbial production systems. Furthermore, in experimental challenge models M2e-based immunity is largely accomplished by IgG and early stage clinical studies have demonstrated that the vaccine is safe. Yet M2e is considered a difficult target to develop as a vaccine: it does not offer sterilizing immunity and its mode of action relies on Fc receptor-mediated effector mechanisms, most likely in concert with alveolar macrophages. It is therefore not straightforward to develop a robust laboratory assay that mimics this mode of action and that could be the basis to define correlates of protection for M2e-vaccines. In a human challenge study with an H3N2 virus, treatment with a monoclonal M2e-specific human IgG was associated with a significant reduction of the total daily symptoms and a faster recovery compared to placebo treatment. The 2009 H1N1 pandemic came too early to evaluate the protective potential of M2e vaccine candidates. If the universal influenza vaccine field incorporates this antigen into next generation vaccines, M2e could prove its merit when the next influenza pandemic strikes.
PMID: 30715367 DOI: 10.1093/infdis/jiz003
[h=1]The Role of M2e in the Development of Universal Influenza Vaccines.[/h] Saelens X[SUP]1,[/SUP][SUP]2,[/SUP][SUP]3[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Two decades ago, the influenza A virus matrix protein 2 ectodomain (M2e) was proposed as a universal influenza A vaccine candidate. Today it still is. M2e is very conserved, poorly immunogenic in the context of natural infections, and can be rendered highly immunogenic by fusing it to almost any carrier that is suitable for use as a vaccine. Numerous studies in laboratory mice, but very few in natural influenza A virus hosts, have demonstrated that M2e-based vaccines can provide protection against any influenza A virus challenge. The production of M2e vaccines is feasible in economic and safe microbial production systems. Furthermore, in experimental challenge models M2e-based immunity is largely accomplished by IgG and early stage clinical studies have demonstrated that the vaccine is safe. Yet M2e is considered a difficult target to develop as a vaccine: it does not offer sterilizing immunity and its mode of action relies on Fc receptor-mediated effector mechanisms, most likely in concert with alveolar macrophages. It is therefore not straightforward to develop a robust laboratory assay that mimics this mode of action and that could be the basis to define correlates of protection for M2e-vaccines. In a human challenge study with an H3N2 virus, treatment with a monoclonal M2e-specific human IgG was associated with a significant reduction of the total daily symptoms and a faster recovery compared to placebo treatment. The 2009 H1N1 pandemic came too early to evaluate the protective potential of M2e vaccine candidates. If the universal influenza vaccine field incorporates this antigen into next generation vaccines, M2e could prove its merit when the next influenza pandemic strikes.
PMID: 30715367 DOI: 10.1093/infdis/jiz003