A Double Mutant Heat-Labile Toxin from Escherichia coli, LT(R192G/L211A), Is an Effective Mucosal Adjuvant for Vaccination against Helicobacter pylori Infection

Helicobacter pylori infection in the stomach is a common cause of peptic ulcer disease and is a strong risk factor for the develop-ment of gastric adenocarcinoma, yet no effective vaccine againstH. pylori infection is available to date. In mice, mucosal vacci-nation withH. pylori antigens when given together with cholera toxin (CT) adjuvant, but not without adjuvant, can induce pro-tective immune responses againstH. pylori infection. However, the toxicity of CT precludes its use as a mucosal adjuvant in humans. We evaluated a recently developed, essentially nontoxic double mutant Escherichia coli heat-labile toxin, LT(R192G/ L211A) (dmLT), as a mucosal adjuvant in an experimentalH. pylori vaccine and compared it to CT in promoting immune re-sponses and protection againstH. pylori infection in mice. Immunization via the sublingual or intragastric route withH. pylori lysate antigens and dmLT resulted in a significant decrease in bacterial load after challenge compared to that in unimmunized infection controls and to the same extent as when using CT as an adjuvant. Cellular immune responses in the sublingually im-munized mice known to correlate with protection were also fully comparable when using dmLT and CT as adjuvants, resulting in enhanced in vitro proliferative and cytokine responses from spleen and mesenteric lymph node cells toH. pylori antigens. Our results suggest that dmLT is an attractive adjuvant for inclusion in a mucosal vaccine againstH. pylori infection. Approximately half of the world’s population is infected withHelicobacter pylori bacteria in the stomach. While most indi-viduals remain asymptomatic, 10 to 15 % develop symptoms such as dyspepsia and peptic ulcers, and chronic infection with H. py