Immunodominant epitope-specific Th1 but not Th17 responses mediate protection against Helicobacter pylori infection following UreB vaccination of BALB/c mice

Abstract

Helicobacter pylori (H. pylori) infects more than half of the world’s population, causing chronic gastritis, peptic ulcers and gastric cancer. Urease B subunit (UreB), a conserved protein of H. pylori, is capable of inducing specific CD4+ T-cell responses and provides protection against this infection. Previous studies have confirmed the effectiveness of rUreB subunit vaccines in generating CD4+ T-cell-mediated protection, but less is known regarding the roles of different subtypes of T-cell immunity, such as Th1, Th2 and Th17, particularly the immunodominant epitopes inducing specific CD4+ T-cell responses, in vaccine-mediated protection. In this study, we demonstrated that the vaccination of BALB/c mice with rUreB resulted in significant antigen-specific Th1 and Th17 immune responses. Importantly, two novel Th epitopes, UreB317–329 and UreB409–421, which are recognized by a major population of CD4+ T cells, were identified in immunized mice. Our results demonstrated that two novel epitopes can simultaneously induce Th1 and Th17 immune responses; however, only the epitope vaccine-induced CD4+ T-cells secreting IFN-γ mediated the protection against H. pylori; cells secreting IL-17A did not. Taken together, our results suggest that two novel immunodominant epitopes can induce Th1 and Th17 immune responses, but only the induced Th1 lymphocytes mediate protection against H. pylori.

The Exopolysaccharide of Lactobacillus fermentum UCO-979C Is Partially Involved in Its Immunomodulatory Effect and Its Ability to Improve the Resistance against Helicobacter pylori Infection

“…The infection of adult immunocompetent mice with H. pylori significantly increased the inflammatory cells infiltrating the stomach mucosa, since control mice displayed no inflammation versus notable inflammatory changes in the infected control mice. Inflammatory infiltrates consisted of neutrophils and mononuclear cells in the lamina propria and around the gastric glands, as has been described in previous publications [27,28]. The inflammation of gastric tissue in L. fermentum UCO-979C-treated mice was milder than that in controls after infection.…”

How Helicobacter pylori senses, targets and interacts with the gastric epithelium

“…Patients with gastric cancer have a very low survival rate after diagnosis, indicating that the best treatment plan is actually prevention or elimination of H. pylori infection (Peek, ). Many attempts to find a vaccine for this bacterium have been made but with only limited success so far (Li et al ., ). In contrast, H. pylori infections generally can be eradicated using well‐established antibiotics (Lee et al ., ).…”

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

“…There is some evidence supporting that Th2 cell responses dominate the protective effect against H. pylori infection (Mohammadi et al, 1997 ; Saldinger et al, 1998 ). However, recent studies demonstrate that Th1 or Th17 cells mediate protection (DeLyria et al, 2009 ; Li et al, 2015 ). Meanwhile, other studies suggested that the protective immunity against H. pylori was mediated by mixed Th cell responses (Liu et al, 2011 ; Chen et al, 2014 ; Yang et al, 2015 ).…”