Purified gamma-irradiated influenza A vaccine demonstrates high immunogenicity and protection against a drifted H1N1 strain.

Although vaccination is recognised as the optimal method to reduce the health burden associated with influenza virus infections, current vaccines regularly demonstrate low efficacy despite annual reformulation. To address the critical need for a more effective vaccine, our group has developed a gamma-irradiated influenza A virus (IAV) vaccine (γ-flu) and illustrated broad-spectrum immunity against drifted and heterosubtypic IAV infections following intranasal vaccination. For clinical development, highly purified vaccine preparations based on clinically relevant IAV isolates are required. Here, we report the structural integrity of a highly purified γ-flu preparation based on A/Brisbane/02/2018-like H1N1pdm09, which was included in recent World Health Organisation (WHO) recommendation for seasonal vaccine formulation. To illustrate immunogenicity and protective efficacy, mice were vaccinated twice via intramuscular injections using low doses of purified γ-flu and challenged with a lethal dose of drifted IAV strain. Analysis of immune serum from vaccinated animals showed significant neutralising antibody responses against both homotypic and closely related drifted IAV strains compared to sera from control unvaccinated mice. This high immunogenicity was also associated with significant protection against a lethal challenge with drifted IAV strain. Overall, this study illustrates the structural integrity and immunogenicity of a highly purified γ-flu vaccine preparation suitable for clinical development.