Malfertheiner P, et al. – This phase 1/2, randomized, placebo-controlled study evaluated the efficacy of a vaccine composed of three recombinant Helicobacter pylori antigens—vacuolating cytotoxin A (VacA), cytotoxin-associated antigen (CagA), and neutrophil-activating protein (NAP)—in prevention of an H. pylori infection following challenge with a CagA-positive strain (BCM 300) in healthy volunteers. Despite increased systemic humoral responses to key H. pylori antigens, additional protection against H. pylori infection after challenge with a CagA-positive strain was not conferred by the vaccine vs placebo. Results showed spontaneous clearance of H. pylori in >50% of participants in the placebo group, suggesting important immune protection in the healthy adult population.

Methods

• Healthy, non-pregnant adults aged 18-40 years who were confirmed negative for H. pylori infection were randomized (3:4)—using a computer-generated list with study numbers to ensure the correct ratio within a block size of seven—to three intramuscular doses of either placebo or vaccine at 0, 1, and 2 months.
• Participants were consecutively assigned in a double-blind manner to existing study numbers of the study protocol, and investigators and participants were blinded to allocation throughout the study.
• Following one month after the third immunization, participants underwent challenge with a CagA-positive H. pylori strain, which, for safety purposes, was initially administered in a subset of participants.
• The efficacy of the vaccine, as measured by the proportion of participants infected with H. pylori 12 weeks after the challenge, was the primary efficacy outcome.
• At the end of the study, participants infected with H pylori were treated for 14 days with combination therapy consisting of a proton pump inhibitor and two antibiotics twice daily.
• At pre-established visits, safety and immunogenicity were monitored.

Results

• A total of 63 patients were randomized: 27 to placebo and 36 to the vaccine.
• Of these participants, 34 (19 in the vaccinated group and 15 in the placebo group) underwent infectious challenge; all but one experienced transient mild-to-moderate epigastric symptoms.
• In the vaccinated group, 6 of 19 (32%) participants and 6 of 15 (40%) participants in the placebo group remained positive for H. pylori 12 weeks after infectious challenge.
• In everyone who remained infected at 12 weeks, eradication was successful.
• In the vaccine group, the geometric mean concentrations of antibodies specific to CagA (202 [95% confidence interval (CI): 69–588] vs 4.73 [95% CI: 1.41–16]; P=0·001), VacA (1469 [95% CI: 838–2577] vs 73 [95% CI: 39–138]; P=0·001), and NAP (208 [95% CI: 139–313] vs 8.01 [95% CI: 5.05–13]; P=0·001) were significantly higher vs the placebo group 12 weeks following infectious challenge.