Oral multivalent epitope vaccine, based on UreB, HpaA, CAT, and LTB, for prevention and treatment of Helicobacter pylori infection in C57BL / 6 mice

Abstract

Background As the resistance of Helicobacter pylori to traditional triple therapy is gradually revealed, an increasing number of people are focusing on vaccine treatments for H. pylori infection. Epitope vaccines are a promising strategy for the treatment of H. pylori infection, and multivalent vaccines will be more effective than monovalent vaccines. Materials and methods In this study, we designed a multivalent vaccine named LHUC, which consists of the adjuvant LTB as well as three Th cell epitopes (HpaA154‐171, UreB237‐251, and UreB546‐561) and five B‐cell epitopes (UreB349‐363, UreB327‐334, CAT394‐405, CAT387‐397, and HpaA132‐141) from UreB, HpaA, and catalase. In BALB/c mice, the specificity and immunogenicity of the fusion peptide LHUC and the neutralization of H. pylori urease and catalase by the specific IgG elicited by LHUC were evaluated. The preventive and therapeutic effects of LHUC were evaluated in C57BL/6 mice infected with H. pylori. Results The results showed that compared with LTB and PBS, LHUC induced specific IgG and IgA antibody production in mice, and IgG antibodies significantly inhibited the H. pylori urease and catalase activities in vitro. Additionally, by detecting the levels of IFN‐γ, IL‐4, and IL‐17 in lymphocyte supernatants, we proved that LHUC could activate Th1, Th2, and Th17 mixed T‐cell immune responses in vivo. Finally, a C57BL/6 mouse model of gastric infection with H. pylori was established. The results showed that compared with the effects of LTB and PBS, the prevention and treatment effects of oral inoculation with LHUC significantly inhibited bacterial colonization. Conclusions In conclusion, LHUC, a multivalent vaccine based on multiple H. pylori antigens, is a promising and safe vaccine that can effectively reduce the colonization of H. pylori in the stomach.

Salivary Biochemistry Associated with Helicobacter Pylori Positivity in Patients with Chronic Gastritis

“…Studies have demonstrated that the naturally occurring antibodies, particularly IgA, could prevent infection of H. pylori. (11) The sIgA improves bacterial opsonization and inhibits bacterial adherence and colonisation. (12) In order to fight off the pathogenic bacteria, the host's adaptive oral immune mechanisms are likely involved in HP infection.…”

“…Various studies have reported that saliva is a noninvasive sample for detection and attractive option for epidemiologic studies because it has been analyzed and obtained easily, collection and testing salivary specimens is fast, painless, convenient, and carries no risk of needle stick injury (10) . The salivary PH and flow rate in study were higher in study group than normal values in healthy control group, the pH value of unstimulated saliva is acidic which ranges between (5.75 -7.05), it becomes more when the flow rate was increased and may reach a PH at high flow rate, in addition to the flow rate, the pH also depends on the salivary proteins concentration, phosphate (PO43−) ions and bicarbonate (HCO3−) that have considerable buffering capacity for maintaining the PH level in saliva (11). The esophago-salivary reflex may be affected by the acidic gastric content that refluxing into esophageal lumen which causes damage to esophageal mucosa, all these changes lead to stimulates salivary secretion and changes the concentration of some of saliva constituents.…”

Detection and Treatment of Helicobacter pylori: Problems and Advances

“…A prophylactic or therapeutic vaccine needs the selection and combination of immunogenic bacterial antigens with effective adjuvants and its administration via an available route [ 109 ]. The main antigens related to vaccines are CagA, VacA, BabA, HpaA, NapA, OipA, GGT, HspA, Omp, and FliD [ 110 ], and their combinations of multivalent epitopes with adjuvants, usually composed of CD4 + and CD8 + epitopes [ 111 ] (e.g., CTB-UE, CWAE vaccine [ 112 ], CFdAE vaccine [ 113 ], FVPE vaccine [ 114 ], HUepi-LTB vaccine [ 115 ], LHUC-LTB [ 116 ], and CTB-HUUC vaccine [ 117 ]). Some vaccines have been developed, such as oral delivery of either whole cell or subunit vaccines in combination with cholera toxin and Escherichia coli enterotoxin as mucosal adjuvant to increase the immunogenicity, oral delivery of live vector vaccines expressing H. pylori antigens to stimulate durable immunity (e.g., avirulent strains of Salmonella and attenuated Listeria monocytogenes ), and intramuscular delivery of H. pylori subunits vaccines with aluminum hydroxide adjuvant [ 118 – 120 ].…”

Discussion on the common controversies of Helicobacter pylori infection

“…Urease is also a main antigen in vaccines, and UreB is considered as the most suitable for urease‐recombinant vaccines 23 . Oral multivalent epitope vaccine combining UreB and Th/B cell epitopes with novel adjuvants was found safe and effective in the mice model 24–26 …”

“…23 Oral multivalent epitope vaccine combining UreB and Th/B cell epitopes with novel adjuvants was found safe and effective in the mice model. [24][25][26] When encountering the suitable niche, H. pylori will establish the persistent colonization, and subsequently cause gastric or extra-gastric diseases. 1%-3% H. pylori infected patients may develop gastric cancer (GC) accounting for 90% of non-cardia GC (NCGC) and 20% of cardia GC (CGC) with adjusted hazard ratios of 5.94 for NCGC and 3.06 for CGC, which accounts for 15% of the total cancer burden globally.…”