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

Abstract

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.

Helicobacter pylori CagA promotes the malignant transformation of gastric mucosal epithelial cells through the dysregulation of the miR‐155/KLF4 signaling pathway

“…Infection with H. pylori , which is characterized as highly pathogenic and difficult to eradicate, is the major cause of GC . However, the molecular mechanisms underlying H. pylori infection‐mediated GC are still largely unknown.…”

Review: Helicobacter: Inflammation, immunology, and vaccines

“…33 Ghasemi et al 34 34 Moreover, vaccinated mice showed a mixed Th1/ Th2/Th17 response and antigen-specific IgG2a/IgG1 production. 35 Increased lymphocyte proliferation and IFNγ, interleukin-4 (IL-4), and interleukin-17 (IL-17) production were also observed in the CTB-HUUC-vaccinated animals. 34 No sign of toxicity was noted in the vaccinated mice.…”

“…34 Another multivalent epitope-based vaccine (CTB-HUUC), comprising CTB adjuvant and tandem copies of B-and T-cell epitopes from H pylori adhesion A subunit (HpaA), urease A subunit (UreA), UreB, and CagA induced significant increased levels of H pylorispecific serum and mucosal antibody responses, when compared with mice immunized with CTB alone or PBS. 35 Increased lymphocyte proliferation and IFNγ, interleukin-4 (IL-4), and interleukin-17 (IL-17) production were also observed in the CTB-HUUC-vaccinated animals. Both oral prophylactic and therapeutic vaccination routes with CTB-HUUC provided significant protection, equivalent to approximately 4-and 2-log decreases in bacterial loads, respectively, against H pylori challenge in BALB/c mice.…”

Immunogenicity and Protection from Receptor-Binding Domains of Toxins as Potential Vaccine Candidates for Clostridium difficile

“…The most important reason for this observation must be that the RBD-TcdA/B vaccine can induce the production of more types and higher levels of RBD-specific antibodies, which can block two toxin RBDs to inhibit the action of the toxins. Moreover, toxins can be used as adjuvant in several research models [39,40]. In our study, we found that the anti-toxin A, but not anti-toxin B, neutralizing antibody titer induced by the RBD-TcdA/B vaccine was much higher than that induced by the single one.…”