The isolation of Helicobacter pylori from the human gastric mucosa in 1982 and the demonstration of its involvement in gastritis, peptic ulcer disease and gastric adenocarcinomas have radically changed our perception of these diseases. H. pylori is a small, spiral, gram-negative bacillus that appears to inhabit the mucous layer overlying the gastric epithelial cells in humans. It produces a potent urease, which, by producing ammonia, may help to neutralize gastric acid, but the mechanism by which the bacteria produces gastric inflammation is not clear as it does not invade the mucosa. Development of atrophy and metaplasia of the gastric mucosa are strongly associated with H. pylori infection. Oxidative and nitrosative stress in combination with inflammation plays an important role in gastric carcinogenesis.
H. pylori has an estimated prevalence of about half the world’s population, possibly reaching up to 70% in developing countries and 20–30% in industrialized countries. Although infected individuals often have histological evidence of gastritis, the vast majority of infections are asymptomatic. Infections seem to be more common with age but, in the tropics, they often occur before the age of 10 years, especially in high-density populations with low socioeconomical status. Transmission is from person-to-person, presumably oral-oral and/or faecal-oral. In the absence of treatment, infection is potentially lifelong. Treatment is based on the use of a proton-pump inhibitor and antibiotics (metronidazole and clarithromycin).
H. pylori has been shown to be heterogeneous at the genomic level with a high variability in some genes. The feasibility of preventive vaccination has been proven in animal models (mice, dogs) using whole cell vaccines as well as subunit vaccines comprising selected antigens such as VacA, CagA, NAP, hsp, urease or catalase. One of the difficulties met in vaccine studies is the absence of correlates of protection; another is to develop a vaccine that will be efficacious at the mucosal level. In humans, several Phase I studies have been conducted using:
recombinant attenuated Salmonellas expressing H. pylori urease, that showed mediocre immunogenicity by the oral route;
an oral whole-cell vaccine adjuvanted with wild-type LT, that was discontinued because of excessive side effects;
purified urease co-administered with LT, also put on hold;
a recombinant VacA, CagA and NAP vaccine in alum that proved to be safe and strongly immunogenic. The companies which were involved are Antex, Acambis and Chiron in the USA and the Commonwealth Serum Labs in Australia.
A prophylactic vaccine would be cost-effective in preventing gastric cancer and duodenal ulcer.