Development of vaccines against Helicobacter pylori

Abstract

Helicobacter pylori is a Gram-negative, microaerophilic bacterium adapted to survive in the stomach of humans where it can cause peptide ulcers and gastric cancer. Although effective antibiotic treatment exists, there is a consensus that vaccines are necessary to limit the severity of this infection. Great progress has been made since its discovery 25 years ago in understanding the virulence factors and several aspects of the pathogenesis of the H. pylori gastric diseases. Several key bacterial factors have been identified: urease, vacuolating cytotoxin, cytotoxin-associated antigen, the pathogenicity island, neutrophil-activating protein, and among others. These proteins, in their native or recombinant forms, have been shown to confer protection against infectious challenge with H. pylori in experimental animal models. It is not known, however, through which effector mechanisms this protection is achieved. Nevertheless, a number of clinical trials in healthy volunteers have been conducted using urease given orally as a soluble protein or expressed in bacterial vectors with limited results. Recently, a mixture of H. pylori antigens was reported to be highly immunogenic in H. pylori-negative volunteers following intramuscular administration of the vaccine with aluminium hydroxide as an adjuvant. These data show that vaccination against this pathogen is feasible. More research is required to understand the immunological mechanisms underlying immune-mediate protection.