Current acellular pertussis (aP) vaccines induce strong antibody and Th2 responses but fail to protect against nasal colonization and transmission of Bordetella pertussis. Furthermore, immunity wanes rapidly after immunization. We have developed a novel adjuvant combination (called LP-GMP), comprising c-di-GMP, an intracellular receptor stimulator of interferon genes (STING) agonist, and LP1569, a TLR2 agonist from B. pertussis, which synergistically induces production of IFN-β, IL-12 and IL-23, and maturation of dendritic cells. Parenteral immunization of mice with an experimental aP vaccine formulated with LP-GMP promoted Th1 and Th17 responses and conferred protection against lung infection with B. pertussis. Intranasal immunization with the same aP vaccine-induced potent B. pertussis-specific Th17 responses and IL-17-secreting respiratory tissue-resident memory (T_RM) CD4 T cells, and conferred a high level of protection against nasal colonization as well as lung infection, which was sustained for at least 10 months. Furthermore, long-term protection against nasal colonization with B. pertussis correlated with the number of IL-17-secreting T_RM cells in nasal tissue. Our study has identified an approach for inducing IL-17-secreting T_RM cells that sustain sterilizing immunity against nasal colonization of mice with B. pertussis, and could form the basis of a third generation pertussis vaccine for humans.

中文翻译：

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通过使用诱导分泌 IL-17 的 TRM 细胞的疫苗佐剂组合进行鼻内免疫，对百日咳博德特氏菌鼻定植的持续保护性免疫。

目前的无细胞百日咳 (aP) 疫苗可诱导强烈的抗体和 Th2 反应，但无法防止百日咳博德特氏菌的鼻定植和传播。此外，免疫接种后免疫力迅速下降。我们开发了一种新型佐剂组合（称为 LP-GMP），其中包含干扰素基因 (STING) 激动剂的胞内受体刺激剂 c-di-GMP 和百日咳杆菌中的 TLR2 激动剂 LP1569，可协同诱导 IFN 的产生-β、IL-12 和 IL-23，以及树突状细胞的成熟。用由 LP-GMP 配制的实验性 aP 疫苗对小鼠进行肠胃外免疫，可促进 Th1 和 Th17 反应，并提供针对百日咳杆菌肺部感染的保护作用。使用相同的 aP 疫苗诱导的强效 B._RM ) CD4 T 细胞，并赋予针对鼻腔定植和肺部感染的高水平保护，持续至少 10 个月。此外，针对百日咳杆菌鼻定植的长期保护与鼻组织中分泌 IL-17 的 T _RM细胞的数量相关。我们的研究已经确定了一种诱导分泌 IL-17 的 T _RM细胞的方法，这些细胞可以维持针对百日咳杆菌小鼠鼻腔定植的杀菌免疫力，并且可以构成第三代人类百日咳疫苗的基础。