OVX836 a recombinant nucleoprotein vaccine inducing cellular responses and protective efficacy against multiple influenza A subtypes

Abstract

Inactivated influenza vaccines (IIVs) lack broad efficacy. Cellular immunity to a conserved internal antigen, the nucleoprotein (NP), has been correlated to protection against pandemic and seasonal influenza and thus could have the potential to broaden vaccine efficacy. We developed OVX836, a recombinant protein vaccine based on an oligomerized NP, which shows increased uptake by dendritic cells and immunogenicity compared with NP. Intramuscular immunization in mice with OVX836 induced strong NP-specific CD4+ and CD8+ T-cell systemic responses and established CD8+ tissue memory T cells in the lung parenchyma. Strikingly, OVX836 protected mice against viral challenge with three different influenza A subtypes, isolated several decades apart and induced a reduction in viral load. When co-administered with IIV, OVX836 was even more effective in reducing lung viral load.

Influenza vaccine: engineered nucleoprotein with improved protective efficacy against multiple strains

Circulating influenza A virus (IAV) strains differ in their surface proteins each year, and vaccines eliciting an immune response to these proteins are often only partially protective. Internal viral proteins, such as the nucleoprotein (NP), are highly conserved, and cellular immunity to NP has been correlated with protection from diverse strains. However, current IAV vaccines induce a poor immune response to NP. In this study, led by Fergal Hill from Osivax, researchers develop an oligomeric version of NP with improved immunogenicity. Vaccination of mice with oligomeric NP results in an improved NP-specific T-cell response, including CD8⁺ tissue memory T cells in the lung, and protects mice against three different IAV subtypes. Co-administration with the currently used inactivated influenza vaccine further improves protection against virus infection in mice. These results encourage further pre-clinical and clinical development for this vaccine candidate.