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Epitope-based vaccine is a promising strategy for therapeutic vaccination against  Helicobacter pylori  ( H. pylori ) infection. A multivalent subunit vaccine containing various antigens from  H. pylori  is superior to a univalent subunit vaccine. However, whether a multivalent epitope-based vaccine is superior to a univalent epitope-based vaccine in therapeutic vaccination against  H. pylori , remains unclear. In this study, a multivalent epitope-based vaccine named CWAE against  H. pylori  urease, neutrophil-activating protein (NAP), heat shock protein 60 (HSP60) and  H. pylori  adhesin A (HpaA) was constructed based on mucosal adjuvant cholera toxin B subunit (CTB), Th1-type adjuvant NAP, multiple copies of selected B and Th cell epitopes (UreA 27–53 , UreA 183–203 , HpaA 132–141 , and HSP60 189–203 ), and also the epitope-rich regions of urease B subunit (UreB 158–251  and UreB 321–385 ) predicted by bioinformatics. Immunological properties of CWAE vaccine were characterized in BALB/c mice model. Its therapeutic effect was evaluated in  H. pylori -infected Mongolian gerbil model by comparing with a univalent epitope-based vaccine CTB-UE against  H. pylori  urease that was constructed in our previous studies. Both CWAE and CTB-UE could induce similar levels of specific antibodies against  H. pylori  urease, and had similar inhibition effect of  H. pylori  urease activity. However, only CWAE could induce high levels of specific antibodies to NAP, HSP60, HpaA, and also the synthetic peptides epitopes (UreB 158–172 , UreB 181–195 , UreB 211–225 , UreB 349–363 , HpaA 132–141 , and HSP60 189–203 ). In addition, oral therapeutic immunization with CWAE significantly reduced the number of  H. pylori  colonies in the stomach of Mongolian gerbils, compared with oral immunization using CTB-UE or  H. pylori  urease. The protection of CWAE was associated with higher levels of mixed CD4 +  T cell (Th cell) response, IgG, and secretory IgA (sIgA) antibodies to  H. pylori .  These results indic ate that a  multivalent epitope-based vaccine including Th and B cell epitopes from various  H. pylori  antigens could be a promising candidate against  H. pylori  infection.

frontiers in cellular and infection microbiology

Oral Immunization with a Multivalent Epitope-Based Vaccine, Based on NAP, Urease, HSP60, and HpaA, Provides Therapeutic Effect on H. pylori Infection in Mongolian gerbils