Intranasal immunization with novel EspA-Tir-M fusion protein induces protective immunity against enterohemorrhagic Escherichia coli O157:H7 challenge in mice

Microb Pathog. 2017 Apr:105:19-24. doi: 10.1016/j.micpath.2017.01.062. Epub 2017 Feb 2.

Abstract

Enterohemorrhagic Escherichia coli (EHEC) O157:H7 causes hemorrhagic colitis and hemolytic uremic syndrome in humans. Due to the risks associated with antibiotic treatment against EHEC O157:H7 infection, vaccines represent a promising method for prevention of EHEC O157:H7 infection. Therefore, we constructed the novel bivalent antigen EspA-Tir-M as a candidate EHEC O157:H7 subunit vaccine. We then evaluated the immunogenicity of this novel EHEC O157:H7 subunit vaccine. Immune responses to the fusion protein administered by intranasal and subcutaneous routes were compared in mice. Results showed higher levels of specific mucosal and systemic antibody responses induced by intranasal as compared to subcutaneous immunization. Intranasal immunization enhanced the concentration of interleukin-4, interleukin-10, and interferon-γ, while subcutaneous immunization enhanced only the latter two. In addition, intranasal immunization protected against EHEC O157:H7 colonization and infection in mice at a rate of 90%.Histopathological analysis revealed that vaccination reduced colon damage, especially when administered intranasally. In contrast, subcutaneous immunization elicited a weak immune response and exhibited a low protection rate. These findings demonstrate that intranasal immunization with the fusion protein induces both humoral and cellular immune (Th1/Th2) responses in mice. The novel EspA-Tir-M novel fusion protein therefore represents a promising subunit vaccine against EHEC O157:H7 infection.

Keywords: Enterohemorrhagic Escherichia coli; Fusion protein; Immunogenicity; Subunit vaccine.

MeSH terms

  • Administration, Intranasal
  • Animals
  • Antibodies, Bacterial / analysis
  • Antibodies, Bacterial / blood
  • Colitis / microbiology
  • Colitis / prevention & control
  • Colon / microbiology
  • Colon / pathology
  • Cytokines / metabolism
  • Disease Models, Animal
  • Escherichia coli Infections / microbiology
  • Escherichia coli Infections / prevention & control*
  • Escherichia coli O157 / immunology*
  • Escherichia coli Proteins / genetics
  • Escherichia coli Proteins / immunology*
  • Escherichia coli Vaccines / administration & dosage
  • Escherichia coli Vaccines / genetics
  • Escherichia coli Vaccines / immunology*
  • Female
  • Immunity, Mucosal
  • Injections, Subcutaneous
  • Mice, Inbred BALB C
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / immunology*
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / immunology*
  • Vaccines, Subunit / administration & dosage
  • Vaccines, Subunit / genetics
  • Vaccines, Subunit / immunology
  • Vaccines, Synthetic / administration & dosage
  • Vaccines, Synthetic / genetics
  • Vaccines, Synthetic / immunology

Substances

  • Antibodies, Bacterial
  • Cytokines
  • Escherichia coli Proteins
  • Escherichia coli Vaccines
  • EspA protein, E coli
  • Receptors, Cell Surface
  • Recombinant Fusion Proteins
  • Tir protein, E coli
  • Vaccines, Subunit
  • Vaccines, Synthetic