Therapeutic efficacy of oral immunization with attenuated Salmonella typhimurium expressing Helicobacter pylori CagA, VacA and UreB fusion proteins in mice model

Vaccine. 2011 Sep 2;29(38):6679-85. doi: 10.1016/j.vaccine.2011.06.099. Epub 2011 Jul 13.

Abstract

Therapeutic vaccination is a desirable alternative for controlling Helicobacter pylori (H. pylori) infection. In the present study, attenuated Salmonella vector vaccines were constructed that expressed fusion proteins complexed with H. pylori CagA, VacA and UreB in different arrangements, and their therapeutic efficacy was evaluated in H. pylori-infected mice. Oral therapeutic immunization with attenuated Salmonella, which expressed the fused protein CVU, significantly decreased H. pylori colonization in the stomach; protection was related to specific CD4(+) T cell Th1 type responses and serum IgG and mucosal sIgA antibody responses. These findings suggested that therapeutic efficacy was related to the arrangement of the fusion protein. It is possible that arrangement decides the expression of recombinant antigen in mice, and the latter results in different therapeutic efficacy. The attenuated Salmonella vector vaccine, which expressed the fused protein arrangement CVU, is superior to others, and could be a candidate vaccine against H. pylori.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Bacterial / analysis
  • Antibodies, Bacterial / blood
  • Antigens, Bacterial / genetics
  • Antigens, Bacterial / immunology*
  • Bacterial Load
  • Bacterial Proteins / genetics
  • Bacterial Proteins / immunology*
  • Bacterial Vaccines / administration & dosage
  • Bacterial Vaccines / genetics
  • Bacterial Vaccines / immunology*
  • CD4-Positive T-Lymphocytes / immunology
  • Cytokines / metabolism
  • Disease Models, Animal
  • Female
  • Helicobacter Infections / therapy*
  • Helicobacter pylori / genetics
  • Helicobacter pylori / immunology*
  • Humans
  • Immunity, Mucosal
  • Immunotherapy / methods
  • Mice
  • Mice, Inbred BALB C
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / immunology
  • Rodent Diseases / therapy
  • Salmonella typhimurium / genetics*
  • Stomach / microbiology
  • Urease / genetics
  • Urease / immunology*
  • Vaccines, Synthetic / administration & dosage
  • Vaccines, Synthetic / genetics
  • Vaccines, Synthetic / immunology

Substances

  • Antibodies, Bacterial
  • Antigens, Bacterial
  • Bacterial Proteins
  • Bacterial Vaccines
  • Cytokines
  • Recombinant Fusion Proteins
  • VacA protein, Helicobacter pylori
  • Vaccines, Synthetic
  • cagA protein, Helicobacter pylori
  • Urease