Chronic Helicobacter pylori infection is the cause of peptic ulcers in a subpopulation of individuals and a risk factor for the development of gastric cancer. A vaccine against H pylori infection can prevent the acquisition of the infection and protect against reinfections. Clinical trials to date evaluating the efficacy of H pylori vaccines in human challenge models have shown moderate to poor protection with difficulties in predicting efficacy. Thus, while further studies are needed to design an effective vaccine, we also need to find relevant correlates for vaccine efficacy. To find immune correlates to vaccine efficacy, the frequencies of neutrophils, eosinophils and inflammatory monocytes and CD4+ T-cell memory and mucosa homing integrin 47+ cells were assessed by flow cytometry in the blood of mice after vaccination. H pylori antigens and cholera toxin or the multiple mutant CT (mmCT) were administered via the sublingual (SL) and intragastric route (IG). The vaccinated mice were infected with H pylori strain SS1 bacteria, and colonization in the stomach and immune responses were evaluated. The H pylori vaccine was effective in reducing bacterial load in the stomach of mice and enhancing immune responses compared to unvaccinated infection controls. In the blood of mice after SL or IG route of vaccination, we observed changes in frequencies of innate and adaptive immune cell subsets compared to infection controls. Remarkably, the frequency of circulating mucosal homing 47+ CD4+ T cells after vaccination correlated with low bacterial load in the stomach of individual mice irrespective of the immunization route. Our study shows that the innate and adaptive immune cell subsets can be measured in the blood after vaccination and that increased frequency of 47+ CD4+ in the blood after immunization could be used as a predictive marker for the efficacy of vaccine against H pylori infection. 2019 The Authors. Helicobacter published by John Wiley & Sons Ltd.