Cross-protection against influenza viruses by chimeric M2e-H3 stalk protein or multi-subtype neuraminidase plus M2e virus-like particle vaccine in ferrets.

Current influenza vaccine is not effective in providing cross-protection against variants. We evaluated the immunogenicity and efficacy of multi-subtype neuraminidase (NA) and M2 ectodomain virus-like particle (m-cNA-M2e VLP) and chimeric M2e-H3 stalk protein vaccines (M2e-H3 stalk) in ferrets. Our results showed that ferrets with recombinant m-cNA-M2e VLP or M2e-H3 stalk vaccination induced multi-vaccine antigen specific IgG antibodies (M2e, H3 stalk, NA), NA inhibition, antibody-secreting cells, and IFN-γ secreting cell responses.

Multivalent and Sequential Heterologous Spike Protein Vaccinations Effectively Induce Protective Humoral Immunity against SARS-CoV-2 Variants.

The emergence of new SARS-CoV-2 variants continues to cause challenging problems for the effective control of COVID-19. In this study, we tested the hypothesis of whether a strategy of multivalent and sequential heterologous spike protein vaccinations would induce a broader range and higher levels of neutralizing antibodies against SARS-CoV-2 variants and more effective protection than homologous spike protein vaccination in a mouse model. We determined spike-specific IgG, receptor-binding inhibition titers, and protective efficacy in the groups of mice that were vaccinated with multivalent recombinant spike proteins (Wuhan, Delta, Omicron), sequentially with heterologous spike protein variants, or with homologous spike proteins.

Supplementation of seasonal vaccine with multi-subtype neuraminidase and M2 ectodomain virus-like particle improves protection against homologous and heterologous influenza viruses in aged mice.

The conventional inactivated split seasonal influenza vaccine offers low efficacy, particularly in the elderly and against antigenic variants. Here, to improve the efficacy of seasonal vaccination for the elderly population, we tested whether supplementing seasonal bivalent (H1N1 + H3N2) split (S) vaccine with M2 ectodomain repeat and multi-subtype consensus neuraminidase (NA) proteins (N1 NA + N2 NA + flu B NA) on a virus-like particle (NA-M2e) would induce enhanced cross-protection against different influenza viruses in aged mice. Immunization with split vaccine plus NA-M2e (S + NA-M2e) increased vaccine-specific IgG antibodies towards T-helper type 1 responses and hemagglutination inhibition titers.