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Vaccination is an increasingly important alternative approach to control  Helicobacter pylori  infection, since  H. pylori  resistance to previously efficacious antibiotic regimens is increased, and  H. pylori  eradication treatment for upper gastrointestinal diseases is becoming less successful. Fortunately, an efficient oral monovalent  H. pylori  vaccine has been developed. However, compared with monovalent vaccines, multivalent vaccines have the potential to induce more effective and comprehensive protection against  H. pylori  infection. In this study, we designed and produced a multivalent epitope-based vaccine cholera toxin B subunit (CTB)-HUUC with the intramucosal adjuvant CTB and tandem copies of B-cell epitopes (HpaA132-141, UreA183-203, and UreB321-339) and T-cell epitopes (HpaA88-100, UreA27-53, UreB229-251, UreB317-329, UreB373-385, UreB438-452, UreB546-561, CagA149-164, and CagA196-217) from  H. pylori  adhesion A subunit (HpaA), urease A subunit (UreA), urease B subunit (UreB), and cytotoxin-associated antigen (CagA). Serum IgG, stomach, and intestine mucosal sIgA from mice after CTB-HUUC vaccination neutralized  H. pylori  urease activity  in vitro . CTB-HUUC vaccination promoted  H. pylori -specific lymphocyte responses and a mixed CD4 +  T cell immune response as indicated by IFN-γ, interleukin-4, and interleukin-17 production in mice. Both oral prophylactic and therapeutic CTB-HUUC vaccinations reduced gastric urease activity and  H. pylori  infection and protected stomachs in mice. Taken together, CTB-HUUC is a promising potent and safe multivalent vaccine in controlling  H. pylori  infection in BALB/c mouse model.

frontiers in immunology

Protection Against Helicobacter pylori Infection in BALB/c Mouse Model by Oral Administration of Multivalent Epitope-Based Vaccine of Cholera Toxin B Subunit-HUUC