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

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

Emily A Hemann, Sang-Moo Kang and Kevin L Legge
The Journal of immunology (1950), Vol.191(5), pp.2486-2494
09/01/2013
DOI: 10.4049/jimmunol.1300954
PMCID: PMC3777857
PMID: 23885108

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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.
Orthomyxoviridae Infections - prevention & control Animals Influenza Vaccines - immunology Influenza A virus - immunology Vaccines, Virus-Like Particle - immunology Mice Mice, Inbred BALB C Viral Matrix Proteins - immunology CD8-Positive T-Lymphocytes - immunology Orthomyxoviridae Infections - immunology

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