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BACKGROUND: Increasing evidence supports a critical role of CD8+ T-cell immunity against influenza. Activation of mucosal CD8+ T cells, particularly tissue-resident memory T (TRM) cells recognizing conserved epitopes would mediate rapid and broad protection. Matrix protein 1 (M1) is a well-conserved internal protein. METHODS: We studied the capacity of modified vaccinia Ankara (MVA)-vectored vaccine expressing nucleoprotein (NP) and M1 (MVA-NP+M1) to activate M1-specific CD8+ T-cell response, including TRM cells, in nasopharynx-associated lymphoid tissue from children and adults. RESULTS: After MVA-NP+M1 stimulation, M1 was abundantly expressed in adenotonsillar epithelial cells and B cells. MVA-NP+M1 activated a marked interferon γ-secreting T-cell response to M1 peptides. Using tetramer staining, we showed the vaccine activated a marked increase in M158-66 peptide-specific CD8+ T cells in tonsillar mononuclear cells of HLA-matched individuals. We also demonstrated MVA-NP+M1 activated a substantial increase in TRM cells exhibiting effector memory T-cell phenotype. On recall antigen recognition, M1-specific T cells rapidly undergo cytotoxic degranulation, release granzyme B and proinflammatory cytokines, leading to target cell killing. CONCLUSIONS: MVA-NP+M1 elicits a substantial M1-specific T-cell response, including TRM cells, in nasopharynx-associated lymphoid tissue, demonstrating its strong capacity to expand memory T-cell pool exhibiting effector memory T-cell phenotype, therefore offering great potential for rapid and broad protection against influenza reinfection.

Original publication




Journal article


J Infect Dis

Publication Date





807 - 819


Influenza, T -ell immunity, antigen-specific T cell, cytotoxic T cell, nasopharynx-associated lymphoid tissue, tissue-resident memory T cells (TRM), vaccine, Adenoids, Adolescent, Adult, CD8-Positive T-Lymphocytes, Cell Degranulation, Cell Proliferation, Cells, Cultured, Child, Child, Preschool, Granzymes, Humans, Immunity, Cellular, Immunologic Memory, Influenza A Virus, H3N2 Subtype, Interferon-gamma, Lymphocyte Activation, Lysosomal-Associated Membrane Protein 1, Nasopharynx, Nucleocapsid Proteins, Palatine Tonsil, Respiratory Mucosa, Vaccines, DNA, Viral Matrix Proteins, Viral Vaccines, Young Adult