A strategy of enhancing the protective efficacy of seasonal influenza vaccines by providing additional immunity to neuraminidase and M2e

It is a high priority to enhance the efficacy of seasonal influenza vaccines based on hemagglutinin (HA) strain-specific neutralizing immunity. Here, we investigated a vaccination strategy of supplementing inactivated split seasonal vaccines with a virus-like particle vaccine containing multi-subtype neuraminidase (NA) and M2 ectodomain (M2e) repeat (NA-M2e) in mice. NA-M2e and split combined vaccine (S + NA-M2e) stimulated a unique pattern of innate immune responses within a day after intramuscular injection of mice. The combined S + NA-M2e vaccination induced enhanced levels of IgG antibodies to viral antigens, hemagglutination inhibiting activities, and humoral and cellular immune responses to NA and M2e. The addition of NA-M2e to split vaccination provided higher efficacy of protection against homologous and heterologous viruses compared to split alone, where NA-M2e significantly contributed to enhancing protection under naïve and primed mouse models. This study supports a vaccination strategy to improve the efficacy of seasonal vaccines by providing additional immunity to NA and M2e.