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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 played in overall VLP-mediated protection was less understood. Work by Emily Hemann and Kevin L. Legge, recently published in the Journal of Immunology and highlighted by an “In this Issue” commentary, demonstrates that intranasal vaccination with a VLP containing the hemagglutinin (HA) and matrix 1 (M1) proteins of influenza virus leads to a significant increase in influenza virus-specific CD8 T cells in the lungs and protection following subsequent exposure to homologous influenza virus strains. Importantly, their results showed that VLP-vaccine induced CD8 T cell mediated protection is not limited to homologous IAV strains but rather that VLP vaccination leads to an increase in protection following exposure to heterosubtypic strains of influenza virus that avoid vaccine-induced neutralizing antibodies but contains conserved, immunodominant CD8 T cell epitopes. Overall, their results suggest that vaccination strategies designed to develop cross-protective CD8 T cell responses may enhance vaccine mediated protection and therein the induction of influenza-specific CD8 T cell responses should be considered in the design of “universal” influenza virus vaccines.
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