Ní Chasaide Caitlín, Schmitt Pauline, Diallo Béré K, Borkner Lisa, Leane Charlotte M, Jazayeri Seyed Davoud, Udayan Sreeram, O'Neill Eoin, Curham Lucy M, Moran Barry, Wilk Mieszko M, Mills Kingston H G
Immune Regulation Research Group, School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland.
Eur J Immunol. 2025 Jul;55(7):e51630. doi: 10.1002/eji.202451630.
Tissue-resident memory T (T) cells play a key role in sustained protective immunity against Bordetella pertussis infection of the nasal mucosa. Current alum-adjuvanted acellular pertussis (aP) vaccines protect against severe pertussis disease but fail to prevent nasal infection with B. pertussis. Here we demonstrate that immunization of mice with an aP vaccine failed to generate respiratory T cells, but did induce antigen-specific CD4 Treg cells that expressed Foxp3, CD49b, PD-1 and LAG-3, and CD8 Treg cells that expressed CD122, PD-1, and IL-10. B. pertussis-specific CD4 and CD8 T cell lines established from aP-immunized mice expressed the regulatory markers and suppressed activation of Th1 and Th17 cells. Blockade of IL-10 signaling during aP immunization or B. pertussis challenge promoted the induction of IL-17-secreting CD4 T responses and enhanced bacterial clearance from the nose. Addition of the adjuvant LP-GMP, comprising TLR2 and STING agonists, to the aP vaccine and delivery by the nasal route promoted the induction of antigen-specific IL-17-producing CD4 T cells and enhanced vaccine efficacy. Our findings demonstrate that aP vaccines suppress the induction of protective T cells in part through the induction of CD4 and CD8 Treg cells, which can be overcome using a potent adjuvant and delivery of the vaccine intranasally.
组织驻留记忆T（Trm）细胞在针对鼻黏膜百日咳博德特氏菌感染的持续保护性免疫中起关键作用。当前的明矾佐剂无细胞百日咳（aP）疫苗可预防严重的百日咳疾病，但无法预防鼻内感染百日咳博德特氏菌。在此，我们证明用aP疫苗免疫小鼠未能产生呼吸道T细胞，但确实诱导了表达Foxp3、CD49b、PD-1和LAG-3的抗原特异性CD4调节性T（Treg）细胞，以及表达CD122、PD-1和IL-10的CD8 Treg细胞。从aP免疫小鼠建立的百日咳博德特氏菌特异性CD4和CD8 T细胞系表达调节性标志物并抑制Th1和Th17细胞的活化。在aP免疫或百日咳博德特氏菌攻击期间阻断IL-10信号传导可促进分泌IL-17的CD4 T反应的诱导，并增强从鼻腔清除细菌的能力。向aP疫苗中添加包含TLR2和STING激动剂的佐剂LP-GMP并通过鼻内途径递送可促进抗原特异性产生IL-17的CD4 T细胞的诱导并提高疫苗效力。我们的研究结果表明，aP疫苗部分通过诱导CD4和CD8 Treg细胞来抑制保护性T细胞的诱导，这可以通过使用强效佐剂和鼻内递送疫苗来克服。
