Systemic Immunization with Unadjuvanted Whole Helicobacter pylori Protects Mice Against Heterologous Challenge

Background: Adjuvant‐free vaccines have many benefits, including decreased cost and toxicity. We examined the protective effect of systemic vaccination with adjuvant‐free formalin‐fixed Helicobacter pylori or bacterial lysate and the ability of this vaccine to induce protection against heterologous challenge. Materials and Methods: Mice were vaccinated subcutaneously with H. pylori 11637 lysate or formalin‐fixed bacteria, with or without ISCOMATRIX^TM adjuvant, then orally challenged with H. pylori SS1. Serum was taken prior to challenge to examine specific antibody levels induced by the vaccinations, and protection was assessed by colony‐forming assay. Results: Vaccination with H. pylori 11637 lysate or formalin‐fixed bacteria delivered systemically induced significantly higher levels of Helicobacter‐specific serum IgG than the control, unvaccinated group and orally vaccinated group. After heterologous challenge with H. pylori SS1, all vaccinated groups had significantly lower levels of colonization compared with unvaccinated, control mice, regardless of the addition of adjuvant or route of delivery. Protection induced by systemic vaccination with whole bacterial preparations, without the addition of adjuvants, was only associated with a mild cellular infiltration into the gastric mucosa, with no evidence of atrophy. Conclusions: Subcutaneous vaccination using unadjuvanted formalin‐fixed H. pylori has the potential to be a simple, cost‐effective approach to the development of a Helicobacter vaccine. Importantly, this vaccine was able to induce protection against heterologous challenge, a factor that would be crucial in any human Helicobacter vaccine. Further studies are required to determine mechanisms of protection and to improve protective ability.