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Vaccine-induced antigen-specific regulatory T cells attenuate the antiviral immunity against acute influenza virus infection.
Mucosal Immunology ( IF 8 ) Pub Date : 2018-07-01 , DOI: 10.1038/s41385-018-0004-9
Pin-Hung Lin , Weng-In Wong , Yi-Lan Wang , Meng-Ping Hsieh , Chia-wen Lu , Chieh-Yu Liang , Sung-Hsiang Jui , Fang-Yi Wu , Pei-Jer Chen , Hung-Chih Yang

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.

中文翻译:

疫苗诱导的抗原特异性调节性 T 细胞减弱了针对急性流感病毒感染的抗病毒免疫。

针对流感病毒保守表位的基于肽的 T 细胞疫苗可以提供针对远缘相关菌株的交叉保护,但它们通常不具有免疫原性。外来抗原特异性调节性 T (Treg) 细胞在亚免疫原性条件下被外周诱导,尽管它们的发育和在疫苗介导的抗病毒免疫中的作用尚不清楚。在这里,我们证明单独使用肽进行初次疫苗接种可显着诱导抗原特异性 Foxp3 +Treg 细胞,通过用无佐剂肽重复接种进一步扩增。某些佐剂,包括 CpG,通过肽疫苗接种抑制抗原特异性 Treg 细胞的诱导和扩增。有趣的是,继发性流感病毒感染显着增加了预先存在的抗原特异性 Treg 细胞的频率,尽管初次感染几乎没有诱导它们。重要的是,疫苗诱导的抗原特异性 Treg 细胞的特异性耗竭促进了流感病毒的清除,表明它们在体内具有抑制作用。通过皮下初免-鼻内-加强策略使用 CpG 佐剂肽进行免疫,限制了肺中抗原特异性 Treg 细胞的募集和积累,并刺激了强大的 T 细胞免疫。最后,用 CpG 佐剂肽或全灭活流感疫苗皮下初免-鼻内-加强免疫可保护小鼠免受异型流感病毒感染。总之,肽疫苗诱导的抗原特异性 Treg 细胞减弱了针对流感病毒感染的抗病毒免疫力。CpG 佐剂肽疫苗可能通过抑制 Treg 发育和增强 T 细胞免疫来提供异型流感保护。
更新日期:2018-02-22
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