A novel chimeric flagellum fused with the multi-epitope vaccine CTB-UE prevents Helicobacter pylori-induced gastric cancer in a BALB/c mouse model

Appl Microbiol Biotechnol. 2015 Nov;99(22):9495-502. doi: 10.1007/s00253-015-6705-z. Epub 2015 Jun 11.

Abstract

Helicobacter pylori (H. pylori) infection causes peptic ulcers, gastric adenocarcinoma, and mucosa-associated lymphoid tissue (MALT) lymphoma. The eradication of H. pylori might be an effective means of preventing gastric cancer. A dual-antigen epitope and dual-adjuvant vaccine called CTB-UE-CF (CCF) was constructed by combining a multi-epitope vaccine CTB-UE with a novel chimeric flagellum (CF) to simultaneously activate Toll-like receptor (TLR) 5-agonist activity and preserve the immunogenicity of H. pylori flagellum FlaA. The evaluation of efficacy to reduce H. pylori colonization was performed using BALB/c mice by oral immunization with a triple dose of this vaccine strain. Two weeks after the last immunization, mice were sacrificed to determine specific antibody levels and proinflammatory cytokine production. To determine the presence of H. pylori, we detected the number of H. pylori by real-time quantitative PCR (qPCR) and measured the urease activity in the gastric tissue. The results showed that the immunogenicity and mucosal immune responses of CCF performed significantly better than those of CTB-UE. This dual-antigen epitope and dual-adjuvant system might greatly contribute to the development of a safe and efficient therapeutic vaccine for humans against H. pylori infection.

Keywords: Adjuvant; Flagellum; Helicobacter pylori; Toll-like receptor 5; Vaccine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic
  • Animals
  • Antibodies, Bacterial / blood
  • Bacterial Proteins / immunology
  • Bacterial Vaccines / immunology*
  • Cytokines / blood
  • Disease Models, Animal
  • Epitopes / immunology
  • Flagella / genetics*
  • Flagella / immunology
  • Helicobacter Infections / immunology*
  • Helicobacter Infections / microbiology
  • Helicobacter Infections / prevention & control*
  • Helicobacter pylori / genetics
  • Helicobacter pylori / growth & development
  • Helicobacter pylori / immunology*
  • Helicobacter pylori / isolation & purification
  • Humans
  • Hydro-Lyases / immunology
  • Immunity, Mucosal
  • Immunization
  • Immunization Schedule
  • Mice, Inbred BALB C
  • Oxidoreductases / immunology
  • Recombinant Fusion Proteins / immunology
  • Stomach Neoplasms / microbiology*
  • Stomach Neoplasms / prevention & control*
  • Toll-Like Receptor 5
  • Urease / chemistry
  • Vaccines, Synthetic / immunology

Substances

  • Adjuvants, Immunologic
  • Antibodies, Bacterial
  • Bacterial Proteins
  • Bacterial Vaccines
  • Cytokines
  • Epitopes
  • FlaA1 protein, Helicobacter pylori
  • Recombinant Fusion Proteins
  • Toll-Like Receptor 5
  • Vaccines, Synthetic
  • Oxidoreductases
  • Urease
  • Hydro-Lyases