Abstract
Despite the importance of immunity against neuraminidase (NA), NA content and immunogenicity are neglected in current influenza vaccines. To address this, a recombinant N1/N2 NA vaccine (NAV) was developed. Stability assays were used to determine optimal temperature and buffer conditions for vaccine storage. The effect of divalent cation-related enhancement of NA stability and activity on N1 and N2 immunogenicity and efficacy against viral challenge was assessed. Differences in activity between N1 and N2 and cation-related activity enhancement did not translate into differences in immunogenicity or efficacy. NAV-vaccinated mice showed robust antibody titers against N1 and N2, and after challenge with influenza A (H1N1) virus, decreased viral titers and decreased antiviral and inflammatory responses by transcriptomic analysis. These findings provide guidance for optimal storage and assessment of NA-based vaccines and confirm the importance of NA in influenza vaccination strategies in attenuating viral replication and limiting inflammatory responses necessary to clear infection.
Highlights
Influenza has precipitated four pandemics in the last century and endemic seasonal influenza continues to be responsible for significant morbidity and mortality worldwide
We evaluated the effect of temperature and buffer on the NA activity of a dual recombinant protein NA vaccine (NAV), and the subsequent impact of NA activity on efficacy and immunogenicity of the vaccine in mice
The findings in this study are helpful in guiding storage practices for NA-based vaccines and explore critical questions regarding the relationships between NA stability, activity, immunogenicity, and potential vaccine efficacy
Summary
Influenza has precipitated four pandemics in the last century and endemic seasonal influenza continues to be responsible for significant morbidity and mortality worldwide. Recombinant protein vaccines have been developed against multiple pathogens, including influenza[11]. Purified NA vaccines (NAVs), and subsequently, recombinant NAVs have demonstrated robust immunogenicity and an ability to protect against lethal infectious challenge in animal models[12]. The protection afforded by NAV was shown to be broader than that of HA vaccines, displaying activity against heterologous strains[13]. Combination purified NAVs have been developed which demonstrated that the inclusion of multiple NA types in a single vaccine did not impair the immune response induced by each type[14]. We evaluated the effect of temperature and buffer on the NA activity of a dual recombinant protein NAV, and the subsequent impact of NA activity on efficacy and immunogenicity of the vaccine in mice
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