The design of vaccines against Helicobacter pylori and their development

Helicobacter pylori is a gram negative, spiral, microaerophylic bacterium t hat infects the stomach of more than 50% of the human population worldwide. It is mostly acquired during childhood and, if not treated, persists chron ically, causing chronic gastritis, peptic ulcer disease, and in some indivi duals, gastric adenocarcinoma and gastric B cell lymphoma. The current ther apy, based on the use of a proton-pump inhibitor and antibiotics, is effica cious but faces problems such as patient compliance, antibiotic resistance, and possible recurrence of infection. The development of an efficacious va ccine against H. pylori would thus offer several advantages. Various approa ches have been followed in the development of vaccines against H. pylori, m ost of which have been based on the use of selected antigens known to be in volved in the pathogenesis of the infection, such as urease, the vacuolatin g cytotoxin (VacA), the cytotoxin-associated antigen (CagA), the neutrophil -activating protein (NAP), and others, and intended to confer protection pr ophylactically and/or therapeutically in animal models of infection. Howeve r, very little is known of the natural history of H. pylori infection and o f the kinetics of the induced immune responses. Several lines of evidence s uggest that H. pylori infection is accompanied by a pronounced Th1-type CD4 (+) T cell response. It appears, however, that after immunization, the anti gen-specific response is predominantly polarized toward a Th2-type response , with production of cytokines that can inhibit the activation of Th1 cells and of macrophages, and the production of proinflammatory cytokines. The e xact effector mechanisms of protection induced after immunization are still poorly understood. The next couple of years will be crucial for the develo pment of vaccines against H. pylori. Several trials are foreseen in humans, and expectations are that most of the questions being asked now on the hos t-microbe interactions will be answered.