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

Epitope-based vaccine is a promising strategy for therapeutic vaccination against () infection. A multivalent subunit vaccine containing various antigens from 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 , remains unclear. In this study, a multivalent epitope-based vaccine named CWAE against urease, neutrophil-activating protein (NAP), heat shock protein 60 (HSP60) and 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, UreA, HpaA, and HSP60), and also the epitope-rich regions of urease B subunit (UreB and UreB) predicted by bioinformatics. Immunological properties of CWAE vaccine were characterized in BALB/c mice model. Its therapeutic effect was evaluated in -infected Mongolian gerbil model by comparing with a univalent epitope-based vaccine CTB-UE against urease that was constructed in our previous studies. Both CWAE and CTB-UE could induce similar levels of specific antibodies against urease, and had similar inhibition effect of urease activity. However, only CWAE could induce high levels of specific antibodies to NAP, HSP60, HpaA, and also the synthetic peptides epitopes (UreB, UreB, UreB, UreB, HpaA, and HSP60). In addition, oral therapeutic immunization with CWAE significantly reduced the number of colonies in the stomach of Mongolian gerbils, compared with oral immunization using CTB-UE or 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 . multivalent epitope-based vaccine including Th and B cell epitopes from various antigens could be a promising candidate against infection.