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

Puksuriwong, Suttida, Ahmed, Muhammad S ORCID: 0000-0001-6163-8102, Sharma, Ravi, Krishnan, Madhan, Leong, Sam, Lambe, Teresa, McNamara, Paul S ORCID: 0000-0002-7055-6034, Gilbert, Sarah C and Zhang, Qibo (2020) 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, 222 (5). pp. 807-819.

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Abstract

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.

Item Type:	Article
Uncontrolled Keywords:	Influenza, T -ell immunity, vaccine, antigen-specific T cell, tissue-resident memory T cells (TRM), nasopharynx-associated lymphoid tissue, cytotoxic T cell
Depositing User:	Symplectic Admin
Date Deposited:	13 Jan 2020 09:58
Last Modified:	19 Jan 2023 00:10
DOI:	10.1093/infdis/jiz593
Open Access URL:	https://doi.org/10.1093/infdis/jiz593
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3070433

Available Versions of this Item

• MVA-NP+M1 vaccine activates mucosal M1-specific T cell immunity and tissue-resident memory T cells in human nasopharynx-associated lymphoid tissue. (deposited 21 Nov 2019 14:31)
  • 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. (deposited 13 Jan 2020 09:58) [Currently Displayed]