Current acellular pertussis vaccines fall short of optimal protection against the human respiratory pathogen Bordetella pertussis resulting in increased incidence of a previously controlled vaccine- preventable disease. Natural infection is known to induce a protective mucosal immunity. Therefore, in this study, we aimed to use acellular pertussis vaccines to recapitulate these mucosal immune responses. We utilized a murine immunization and challenge model to characterize the efficacy of intranasal immunization (IN) with DTaP vaccine or DTaP vaccine supplemented with curdlan, a known Th1/Th17 promoting adjuvant. Protection from IN delivered DTaP was compared to protection mediated by intraperitoneal injection of DTaP and whole-cell pertussis vaccines. We tracked fluorescently labeled DTaP after immunization and detected that DTaP localized preferentially in the lungs while DTaP with curdlan was predominantly in the nasal turbinates. IN immunization with DTaP, with or without curdlan adjuvant, resulted in anti-B. pertussis and anti-pertussis toxin IgG titers at the same level as intraperitoneally administered DTaP. IN immunization was able to protect against B. pertussis challenge and we observed decreased pulmonary pro-inflammatory cytokines, neutrophil infiltrates in the lung, and bacterial burden in the upper and lower respiratory tract at day 3 post challenge. Furthermore, IN immunization with DTaP triggered mucosal immune responses such as production of B. pertussis-specific IgA, and increased IL-17A. Together, the induction of a mucosal immune response and humoral antibody-mediated protection associated with an IN administered DTaP and curdlan adjuvant warrant further exploration as a pertussis vaccine candidate formulation.

当前的脱细胞百日咳疫苗没有针对人类呼吸道病原体百日咳博德特氏菌的最佳保护导致先前控制的疫苗可预防疾病的发生率增加。已知自然感染可诱导保护性粘膜免疫。因此，在这项研究中，我们旨在使用脱细胞百日咳疫苗来概括这些粘膜免疫反应。我们利用鼠类免疫和攻击模型来表征鼻内免疫（IN）的DTaP疫苗或DTaP疫苗补充的可德兰（一种已知的Th1 / Th17促进佐剂）的功效。将针对IN递送的DTaP的保护与通过腹膜内注射DTaP和全细胞百日咳疫苗介导的保护进行了比较。免疫后，我们追踪了荧光标记的DTaP，并检测到DTaP优先定位在肺中，而含有柯德兰的DTaP主要出现在鼻甲中。在DTaP免疫中，B.百日咳和抗百日咳毒素IgG的滴度与腹膜内给予DTaP的浓度相同。IN免疫能够预防百日咳博德特氏菌攻击，我们在攻击后第3天观察到肺促炎性细胞因子减少，肺中性粒细胞浸润减少以及上下呼吸道细菌负荷增加。此外，用DTaP进行的IN免疫引发了粘膜免疫应答，例如百日咳博德特氏菌特异性IgA的产生和IL-17A的增加。总之，与IN施用的DTaP和柯德兰佐剂相关的粘膜免疫应答的诱导和体液抗体介导的保护值得进一步探索作为百日咳疫苗候选制剂。