Intranasal acellular pertussis vaccine provides mucosal immunity and protects mice from Bordetella pertussis
Intranasal acellular pertussis vaccine provides mucosal immunity and protects mice from Bordetella pertussis
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DOI：
10.1038/s41541-019-0136-2
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发表时间：
2019-10-03
期刊：
影响因子：
9.2
通讯作者：
Damron, F. Heath
中科院分区：
文献类型：
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作者：
Boehm, Dylan T.;Wolf, M. Allison;Damron, F. Heath
目前的无细胞百日咳疫苗不能最佳地保护人类呼吸道病原体百日咳博德特氏菌，导致先前控制的疫苗可预防疾病的发病率增加。已知自然感染诱导保护性粘膜免疫。因此，在这项研究中，我们的目的是使用无细胞百日咳疫苗来重现这些粘膜免疫反应。我们利用小鼠免疫和攻击模型来表征用DTaP疫苗或补充有可德兰（一种已知的Th 1/Th 17促进佐剂）的DTaP疫苗鼻内免疫（IN）的功效。将IN递送的DTaP的保护与腹膜内注射DTaP和全细胞百日咳疫苗介导的保护进行比较。我们在免疫后追踪荧光标记的DTaP，并检测到DTaP优先定位在肺中，而DTaP与可德兰主要在鼻甲中。用DTaP（有或没有可得兰佐剂）IN免疫产生抗B。百日咳和抗百日咳毒素IgG滴度与腹腔内注射DTaP的水平相同。IN免疫能够保护免受B。在百日咳激发后第3天，我们观察到肺促炎细胞因子、肺中嗜中性粒细胞浸润和上呼吸道和下呼吸道中的细菌负荷减少。此外，用DTaP进行IN免疫引发粘膜免疫应答，例如产生B。百日咳特异性伊加和增加的IL-17 A。总之，与IN施用的DTaP和凝胶多糖佐剂相关的粘膜免疫应答和体液抗体介导的保护的诱导保证了作为百日咳疫苗候选制剂的进一步探索。
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.