Immunogenicity of 987P fimbriae of enterotoxigenic Escherichia coli surface-displayed on Lactobacillus casei

Res Vet Sci. 2020 Feb:128:308-314. doi: 10.1016/j.rvsc.2019.12.016. Epub 2019 Dec 24.

Abstract

As most pathogens invade the bodies through the mucosa, it is crucial to develop vaccines that induce mucosal immunity. To this end, we generated a safe and effective vaccine candidate that displayed fimbrial protein 987P of enterotoxigenic Escherichia coli (ETEC) on the surface of Lactobacillus casei (L.casei) CICC 6105 by using poly-γ-glutamate synthetase A (PgsA) as an anchoring matrix. After gavage inoculation of the recombinant strain pLA-987P/L.casei into specific-pathogen-free (SPF) BALB/c mice, high levels of mucosal immunoglobulin A (IgA) were induced in fecal samples, intestine and lung lavage fluids and systemic immunoglobulin G of IgG subclasses (IgG1, IgG2b, and IgG2a) was produced in serum. T-cell proliferation assays showed the stimulation index (SI) of the groups immunized with pLA-987P/L.casei to be significantly higher than that of the control group. The recombinant L.casei promoted T cells to produce both Th1 and Th2 cytokines, while the number of splenic IL-4 Spot forming cells (SFC) exceeded the number of IFN-γ SFC by 2.26-fold (P < .01). >83.3% of the vaccinated mice were protected from challenge with a lethal dose of virulent strain C83916. These results indicate that the recombinant L.casei expressing ETEC 987P fimbrial protein could elicit a protective immune response against ETEC 987P infection effectively.

Keywords: 987P fimbrial protein; Enterotoxigenic Escherichia coli (ETEC); Lactobacillus casei; Mucosal immunity; Oral vaccination.

MeSH terms

  • Adhesins, Escherichia coli / genetics
  • Adhesins, Escherichia coli / immunology*
  • Administration, Oral
  • Animals
  • Antigens, Heterophile
  • Enterotoxigenic Escherichia coli / immunology*
  • Escherichia coli Proteins / genetics
  • Escherichia coli Proteins / immunology
  • Escherichia coli Vaccines / biosynthesis*
  • Escherichia coli Vaccines / immunology
  • Fimbriae Proteins / genetics
  • Fimbriae Proteins / immunology*
  • Immunity, Humoral
  • Immunity, Mucosal
  • Immunogenicity, Vaccine
  • Lacticaseibacillus casei / genetics
  • Lacticaseibacillus casei / immunology*
  • Mice
  • Mice, Inbred BALB C
  • Microorganisms, Genetically-Modified / immunology*
  • Transformation, Bacterial / genetics
  • Transformation, Bacterial / immunology
  • Vaccination / methods

Substances

  • Adhesins, Escherichia coli
  • Antigens, Heterophile
  • Escherichia coli Proteins
  • Escherichia coli Vaccines
  • antigen 987P, E coli
  • Fimbriae Proteins