Modified Vaccinia Ankara-Vectored Vaccine Expressing Nucleoprotein and Matrix Protein 1 (M1) Activates Mucosal M1-Specific T-Cell Immunity and Tissue-Resident Memory T Cells in Human Nasopharynx-Associated Lymphoid Tissue.

Suttida Puksuriwong, Muhammad S Ahmed, Ravi Sharma, Madhan Krishnan, Sam Leong, Teresa Lambe, Paul S McNamara, Sarah C Gilbert, Qibo Zhang

The Journal of infectious diseases 2020 Aug 04

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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. 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. 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. 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. © The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America.

Citation

Suttida Puksuriwong, Muhammad S Ahmed, Ravi Sharma, Madhan Krishnan, Sam Leong, Teresa Lambe, Paul S McNamara, Sarah C Gilbert, Qibo Zhang. Modified Vaccinia Ankara-Vectored Vaccine Expressing Nucleoprotein and Matrix Protein 1 (M1) Activates Mucosal M1-Specific T-Cell Immunity and Tissue-Resident Memory T Cells in Human Nasopharynx-Associated Lymphoid Tissue. The Journal of infectious diseases. 2020 Aug 04;222(5):807-819