Systemic priming and intranasal booster with a BcfA-adjuvanted acellular pertussis vaccine generates CD4+ IL-17+ nasal tissue resident T cells and reduces B. pertussis nasal colonization.
Systemic priming and intranasal booster with a BcfA-adjuvanted acellular pertussis vaccine generates CD4+ IL-17+ nasal tissue resident T cells and reduces B. pertussis nasal colonization.
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DOI：
10.3389/fimmu.2023.1181876
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发表时间：
2023
影响因子：
7.3
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中科院分区：
文献类型：
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由百日咳博德特氏菌引起的百日咳的复发需要新的疫苗和疫苗接种策略来对抗这种疾病。铝佐剂无细胞百日咳疫苗（aPV）肌内注射可减少免疫动物和人类肺部的细菌数量，但不能减少鼻腔定植。因此，aPV免疫的个体是社区传播的来源。我们先前表明，通过添加Th 1/17极化佐剂博德特氏菌定殖因子A（BcfA）来修饰商业aPV（Boostrix）减弱了由明矾引起的Th 2应答，并加速了B的清除。小鼠肺部的百日咳病毒。在这里，我们测试了具有全身引发和粘膜加强（引发-拉）的异源免疫策略是否会减少鼻定殖。将成年雄性和雌性小鼠肌内（i.m.）与aPV或aPV/BcfA一起，并且i. m.或鼻内（i.n.）同样的配方。通过流式细胞术定量呼吸道中的组织驻留记忆（TRM）反应，并通过ELISA定量粘膜和全身抗体。免疫和未处理小鼠经i.n.在攻毒后第1-14天计数鼻和肺中的百日咳博德特氏菌和细菌负荷。我们发现Boostrix加BcfA（aPV/BcfA）的初免-拉免免疫在鼻中产生IFNγ+和IL-17+ CD 4+肺驻留记忆T细胞（TRM）以及CD 4 +IL-17+ TRM。相反，通过相同途径单独递送的aPV在肺和鼻中产生IL-5+ CD 4+驻留记忆T细胞。重要的是，鼻定植仅在通过引发-拉方案用aPV/BcfA免疫的小鼠中减少。这些结果表明，由aPV/BcfA产生的TH 17极化TRM可以减少鼻腔定植，从而防止百日咳传播和随后的复发。
Resurgence of pertussis, caused by Bordetella pertussis, necessitates novel vaccines and vaccination strategies to combat this disease. Alum-adjuvanted acellular pertussis vaccines (aPV) delivered intramuscularly reduce bacterial numbers in the lungs of immunized animals and humans, but do not reduce nasal colonization. Thus, aPV-immunized individuals are sources of community transmission. We showed previously that modification of a commercial aPV (Boostrix) by addition of the Th1/17 polarizing adjuvant Bordetella Colonization Factor A (BcfA) attenuated Th2 responses elicited by alum and accelerated clearance of B. pertussis from mouse lungs. Here we tested whether a heterologous immunization strategy with systemic priming and mucosal booster (prime-pull) would reduce nasal colonization. Adult male and female mice were immunized intramuscularly (i.m.) with aPV or aPV/BcfA and boosted either i.m. or intranasally (i.n.) with the same formulation. Tissue-resident memory (TRM) responses in the respiratory tract were quantified by flow cytometry, and mucosal and systemic antibodies were quantified by ELISA. Immunized and naïve mice were challenged i.n. with Bordetella pertussis and bacterial load in the nose and lungs enumerated at days 1-14 post-challenge. We show that prime-pull immunization with Boostrix plus BcfA (aPV/BcfA) generated IFNγ+ and IL-17+ CD4+ lung resident memory T cells (TRM), and CD4+IL-17+ TRM in the nose. In contrast, aPV alone delivered by the same route generated IL-5+ CD4+ resident memory T cells in the lungs and nose. Importantly, nasal colonization was only reduced in mice immunized with aPV/BcfA by the prime-pull regimen. These results suggest that TH17 polarized TRM generated by aPV/BcfA may reduce nasal colonization thereby preventing pertussis transmission and subsequent resurgence.