Adjuvants for Helicobacter pylori vaccines: Outer membrane vesicles provide an alternative strategy.

Helicobacter pylori (H. pylori) is a gram-negative, spiral-shaped bacterium that colonizes the human stomach, leading to various gastric diseases. The efficacy of traditional treatments, such as bismuth-based triple and quadruple therapies, has been reduced due to increasing antibiotic resistance and drug toxicity. As a result, the development of effective vaccines was proposed to control H. pylori-induced infections; however, one of the primary challenges is the lack of potent adjuvants. Although various adjuvants, both toxic (e.g. cholera toxin and Escherichia coli heat-labile toxin) and non-toxic (e.g. aluminum and propolis), have been tested for vaccine development, no clinically favorable adjuvants have been identified due to high toxicity, weak immunostimulatory effects, inability to elicit specific immune responses, or latent side effects. Outer membrane vesicles (OMVs), mainly secreted by gram-negative bacteria, have emerged as promising candidates for H. pylori vaccine adjuvants due to their potential applications. OMVs enhance mucosal immunity and Th1 and Th17 cell responses, which have been recognized to have protective effects and guarantee safety and efficacy. The development of an effective vaccine against H. pylori infection is ongoing, with clinical trials expected in the future.