Helicobacter pylori causes chronic gastric infection that can lead to peptic ulcers and is an identified risk factor for gastric cancer development. Although much effort has been put into the development of a Helicobacter pylori vaccine over the last three decades, none has yet reached clinical application. Specific challenges pertaining to effective H. pylori vaccine development include the lack of proven vaccine-effective antigens and safe mucosal adjuvants to enhance local immune responses as well as the lack of accepted correlates of protection. Herein, we demonstrate that prophylactic intragastric immunisation with a whole-cell killed H. pylori antigen administered together with the non-toxic oral adjuvant α-galactosylceramide (α-GalCer) induced effective immune protection against H. pylori infection in mice, which was of similar magnitude as when using the “gold standard” cholera toxin as adjuvant. We further describe that this α-GalCer-adjuvanted vaccine formulation elicited strong intestinal and systemic Th1 responses as well as significant antigen-specific mucosal and systemic antibody responses. Finally, we report that the protective intestinal Th1 responses induced by α-GalCer are dependent on CD1d, IL-1R as well as IL-17R signalling. In summary, our results show that α-GalCer is a promising adjuvant for inclusion in an oral vaccine against H. pylori infection.

幽门螺杆菌引起慢性胃部感染，可导致消化性溃疡，是胃癌发展的公认危险因素。尽管在过去的三十年中在开发幽门螺杆菌疫苗上投入了大量精力，但尚无临床应用。与有效的幽门螺杆菌疫苗开发有关的具体挑战包括缺乏经过验证的疫苗有效抗原和增强局部免疫应答的安全粘膜佐剂，以及缺乏公认的保护关联。在这里，我们证明了用全细胞杀死的幽门螺杆菌的预防性胃内免疫抗原与无毒口服佐剂α半乳糖苷（α-神经酰胺）相对于诱导有效的免疫保护一起给药H.在小鼠中幽门螺杆菌感染，采用了“金标准”霍乱毒素作为佐剂时，其为相似的幅度。我们进一步描述，这种α-GalCer佐剂疫苗制剂引起强烈的肠道和全身Th1反应以及显着的抗原特异性粘膜和全身抗体反应。最后，我们报道了α-GalCer诱导的保护性肠道Th1反应取决于CD1d，IL-1R和IL-17R信号传导。总之，我们的结果表明，α-GalCer是一种有希望的佐剂，可用于抗幽门螺杆菌感染的口服疫苗中。