An oral alpha-galactosylceramide adjuvanted Helicobacter pylori vaccine induces protective IL-1R-and IL-17R-dependent Th1 responses

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 alpha-galactosylceramide (alpha-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 alpha-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 alpha-GalCer are dependent on CD1d, IL-1R as well as IL-17R signalling. In summary, our results show that alpha-GalCer is a promising adjuvant for inclusion in an oral vaccine against H. pylori infection.