BPZE1 is a live attenuated Bordetella pertussis vaccine for nasal administration to mimic the natural route of infection. Here, we studied the mechanism of BPZE1-induced immunity in the murine nasal cavity in contrast to acellular vaccine (aPV), although both vaccines protected against lung colonization. Transfer of splenocytes or serum from BPZE1-vaccinated or aPV-vaccinated mice protected naïve mice against lung colonization but not against nasal colonization. However, transfer of nasal washes from BPZE1-vaccinated mice resulted in protection against nasal colonization, which was lost in IgA-deficient or poly-Ig receptor-deficient mice, indicating that it depends on secretory IgA (SIgA) induction induced in the nose. BPZE1-induced protection against nasal colonization was long-lived despite the relatively rapid decay of SIgA, indicating a potent BPZE1-induced local memory response, likely due to CD4⁺ tissue-resident memory T cells induced in the nose by BPZE1. These cells produced interleukin-17 (IL-17), known to be important for SIgA secretion. Furthermore, BPZE1 failed to protect Il17^-/- mice against nasal colonization by B. pertussis and induced only background levels of nasal SIgA. Thus, our results show important differences in the protective mechanism between the upper and the lower murine respiratory tract and demonstrate an IL-17-dependent SIgA-mediated mechanism of BPZE1-induced protection against B. pertussis nasopharyngeal colonization.

中文翻译：

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IL-17 依赖性 SIgA 介导的 BPZE1 减毒活疫苗对鼻腔百日咳博德特氏菌感染的保护作用。

BPZE1 是一种用于鼻腔给药以模拟自然感染途径的百日咳博德特氏菌减毒活疫苗。在这里，我们研究了 BPZE1 在小鼠鼻腔中诱导的免疫机制，与无细胞疫苗 (aPV) 相比，尽管这两种疫苗都可以防止肺定植。从 BPZE1 疫苗接种或 aPV 疫苗接种的小鼠转移脾细胞或血清可保护幼稚小鼠免受肺定植，但不能防止鼻定植。然而，从 BPZE1 疫苗接种的小鼠转移鼻洗液可防止鼻定植，这在 IgA 缺陷或多聚 Ig 受体缺陷小鼠中丧失，表明它依赖于在鼻子中诱导的分泌性 IgA (SIgA) 诱导。尽管 SIgA 衰减相对较快，但 BPZE1 诱导的针对鼻定植的保护作用是长期存在的，⁺ BPZE1 在鼻子中诱导的组织驻留记忆 T 细胞。这些细胞产生白细胞介素 17 (IL-17)，已知其对 SIgA 分泌很重要。此外，BPZE1 未能保护 Il17 ^{-/ -}小鼠免受百日咳杆菌的鼻腔定植，并且仅诱导背景水平的鼻腔 SIgA。因此，我们的结果显示了小鼠上呼吸道和下呼吸道之间保护机制的重要差异，并证明了 IL-17 依赖性 SIgA 介导的 BPZE1 诱导的针对百日咳杆菌鼻咽定植保护的机制。