Protective CD8 T cell mediated immunity against influenza A virus infection following influenza virus-like particle vaccination

摘要

The development of influenza A virus (IAV) vaccines capable of inducing cytotoxic CD8 T cell responses could potentially provide superior, long-term protection against multiple, heterologous strains of IAV. While prior studies have demonstrated the effectiveness of baculovirus-derived virus-like particle (VLP) vaccination in generating antibody-mediated protection, what role CD8 T cell immunity plays in overall VLPmediated protection is less understood. Herein we demonstrate that intranasal vaccination of mice with a VLP containing the hemagglutinin (HA) and matrix 1 (M1) proteins of influenza virus A/PR/8/34 leads to a significant increase in HA533-specific CD8 T cells in the lungs and protection following subsequent homologous challenge with IAV. VLP-mediated protection was significantly reduced by CD8 T cell depletion, indicating a critical role for CD8 T cells in contributing to protective immunity. Importantly, our results show VLP-vaccine induced CD8 T cell mediated protection is not limited to homologous IAV strains. VLP vaccination leads to an increase in protection following heterosubtypic challenge with a strain of IAV that avoids vaccine-induced neutralizing antibodies but contains conserved, immunodominant CD8 T cell epitopes. Overall, our results demonstrate the ability of influenza protein-containing VLPs to prime IAV-specific CD8 T cell responses, which contribute to protection from homo- and heterosubtypic influenza A virus infections. These results further suggest that vaccination strategies focused on the development of cross-protective CD8 T cell responses may contribute to the development of “universal” IAV vaccines.