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
| العنوان: | 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 |
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| المؤلفون: | Sam Leong, Qibo Zhang, Muhammad S Ahmed, Ravi Sharma, Suttida Puksuriwong, Teresa Lambe, Sarah C. Gilbert, Madhan Krishnan, Paul S. McNamara |
| المصدر: | The Journal of Infectious Diseases The Journal of infectious diseases |
| بيانات النشر: | Oxford University Press (OUP), 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | 0301 basic medicine, Modified vaccinia Ankara, Palatine Tonsil, CD8-Positive T-Lymphocytes, Lymphocyte Activation, T -ell immunity, Cell Degranulation, Granzymes, Epitope, 0302 clinical medicine, Interferon, vaccine, Nasopharynx, Vaccines, DNA, Immunology and Allergy, Cytotoxic T cell, Child, Cells, Cultured, Immunity, Cellular, Chemistry, Degranulation, Nucleocapsid Proteins, AcademicSubjects/MED00290, Infectious Diseases, Cell killing, Child, Preschool, Viruses, medicine.drug, Adult, antigen-specific T cell, Adolescent, Respiratory Mucosa, Viral Matrix Proteins, Major Articles and Brief Reports, Interferon-gamma, Young Adult, 03 medical and health sciences, Lysosomal-Associated Membrane Protein 1, medicine, Humans, AcademicSubjects/MED00860, tissue-resident memory T cells (TRM), Cell Proliferation, Influenza A Virus, H3N2 Subtype, Viral Vaccines, Molecular biology, Influenza, Granzyme B, 030104 developmental biology, Adenoids, nasopharynx-associated lymphoid tissue, Immunologic Memory, CD8, cytotoxic T cell, 030215 immunology |
| الوصف: | 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. Modified vaccinia Ankara–vectored vaccine expressing nucleoprotein and matrix protein 1 (MVA-NP+M1) activates a substantial increase in anti-influenza M1-specific T cells, including fast-reacting tissue-resident memory T cells in human nasopharynx mucosal tissue. It is therefore a promising mucosal vaccine candidate. |
| وصف الملف: | application/pdf |
| تدمد: | 1537-6613 0022-1899 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::2dc0fd7df807ab28ac1f3d7cabd9aac4Test https://doi.org/10.1093/infdis/jiz593Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....2dc0fd7df807ab28ac1f3d7cabd9aac4 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15376613 00221899 |
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