title: Protective CD8 T cell-mediated immunity against influenza A virus infection following influenza virus-like particle vaccination.
abstract: 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. Although prior studies demonstrated the effectiveness of baculovirus-derived virus-like particle (VLP) vaccination in generating Ab-mediated protection, the role that CD8 T cell immunity plays in overall VLP-mediated protection is less-well understood. In this article, we demonstrate that intranasal vaccination of mice with a VLP containing the hemagglutinin and matrix 1 proteins of IAV/PR/8/34 leads to a significant increase in hemagglutinin 533-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 protective immunity. Importantly, our results show that 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 Abs 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 that contribute to protection from homo- and heterosubtypic IAV 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.
authors.affiliation: Department of Pathology and Interdisciplinary Graduate Program in Immunology, University of Iowa, Iowa City, IA 52242, USA.
authors.forename: Emily A
authors.initials: EA
authors.lastname: Hemann
authors.forename: Sang-Moo
authors.initials: SM
authors.lastname: Kang
authors.forename: Kevin L
authors.initials: KL
authors.lastname: Legge
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D009980:Influenza A virus / Q000276:immunology*; D007252:Influenza Vaccines / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009976:Orthomyxoviridae Infections / Q000276:immunology* / Q000517:prevention & control; D058425:Vaccines, Virus-Like Particle / Q000276:immunology*; D014763:Viral Matrix Proteins / Q000276:immunology
chemical_list: D007252:Influenza Vaccines; D058425:Vaccines, Virus-Like Particle; D014763:Viral Matrix Proteins