https://scholars.lib.ntu.edu.tw/handle/123456789/568338
標題: | Vaccine-induced antigen-specific regulatory T cells attenuate the antiviral immunity against acute influenza virus infection | 作者: | Lin, Pin-Hung Wong, Weng-In Wang, Yi-Lan Hsieh, Meng-Ping CHIA-WEN LU Liang, Chieh-Yu Jui, Sung-Hsiang Wu, Fang-Yi PEI-JER CHEN HUNG-CHIH YANG |
公開日期: | 2018 | 出版社: | Nature Publishing Group | 卷: | 11 | 期: | 4 | 起(迄)頁: | 1239-1253 | 來源出版物: | Mucosal Immunology | 摘要: | Peptide-based T cell vaccines targeting the conserved epitopes of influenza virus can provide cross-protection against distantly related strains, but they are generally not immunogenic. Foreign antigen-specific regulatory T (Treg) cells are induced under subimmunogenic conditions peripherally, although their development and role in vaccine-mediated antiviral immunity is unclear. Here, we demonstrated primary vaccination with peptides alone significantly induced antigen-specific Foxp3+ Treg cells, which were further expanded by repeated vaccination with unadjuvanted peptides. Certain adjuvants, including CpG, suppressed the induction and expansion of antigen-specific Treg cells by peptide vaccination. Interestingly, secondary influenza virus infection significantly increased the frequency of preexisting antigen-specific Treg cells, although primary infection barely induced them. Importantly, specific depletion of vaccine-induced antigen-specific Treg cells promoted influenza viral clearance, indicating their inhibitory role in vivo. Immunization with CpG-adjuvanted peptides by the subcutaneous prime-intranasal-boost strategy restricted the recruitment and accumulation of antigen-specific Treg cells in lung, and stimulated robust T cell immunity. Finally, subcutaneous prime-intranasal-boost immunization with CpG-adjuvanted peptides or whole-inactivated influenza vaccines protected mice from heterosubtypic influenza virus infection. In conclusion, antigen-specific Treg cells induced by peptide vaccines attenuate the antiviral immunity against influenza virus infection. CpG-adjuvanted peptide vaccines provide heterosubtypic influenza protection probably by inhibiting Treg development and enhancing T cell immunity. ? 2018 Society for Mucosal Immunology. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-85042216681&doi=10.1038%2fs41385-018-0004-9&partnerID=40&md5=1242a04f7944550fa726a51792c060da https://scholars.lib.ntu.edu.tw/handle/123456789/568338 |
ISSN: | 1933-0219 | DOI: | 10.1038/s41385-018-0004-9 | SDG/關鍵字: | influenza vaccine; transcription factor FOXP3; virus antigen; epitope; immunological adjuvant; influenza vaccine; oligodeoxyribonucleotide; subunit vaccine; virus antigen; animal experiment; animal model; animal tissue; antigen specificity; Article; cellular immunity; controlled study; in vivo study; infant; influenza; influenza vaccination; mouse; nonhuman; priority journal; regulatory T lymphocyte; viral clearance; virus attenuation; virus immunity; acute disease; animal; C57BL mouse; human; immunological memory; immunology; immunosuppressive treatment; influenza; lymphocyte activation; Orthomyxoviridae; orthomyxovirus infection; physiology; regulatory T lymphocyte; secondary immunization; transgenic mouse; Acute Disease; Adjuvants, Immunologic; Animals; Antigens, Viral; Epitopes, T-Lymphocyte; Humans; Immunization, Secondary; Immunologic Memory; Immunosuppression; Influenza Vaccines; Influenza, Human; Lymphocyte Activation; Mice; Mice, Inbred C57BL; Mice, Transgenic; Oligodeoxyribonucleotides; Orthomyxoviridae; Orthomyxoviridae Infections; T-Lymphocytes, Regulatory; Vaccines, Subunit |
顯示於: | 臨床醫學研究所 |
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