A novel vaccine strategy against Brucellosis using Brucella abortus multi-epitope OMPs vaccine based on Lactococcus lactis live bacterial vectors

Int Immunopharmacol. 2024 Jun 15:134:112204. doi: 10.1016/j.intimp.2024.112204. Epub 2024 May 3.

Abstract

Brucella infections typically occur in mucosal membranes, emphasizing the need for mucosal vaccinations. This study evaluated the effectiveness of orally administering Lactococcus lactis (L. lactis) for producing the Brucella abortus multi-epitope OMPs peptide. A multi-epitope plasmid was generated through a reverse vaccinology method, and mice were administered the genetically modified L. lactis orally as a vaccine. The plasmid underwent digestion, synthesizing a 39 kDa-sized protein known as OMPs by the target group. The sera of mice that were administered the pNZ8124-OMPs-L. lactis vaccine exhibited a notable presence of IgG1 antibodies specific to outer membrane proteins (OMPs), heightened levels of interferon (IFN-λ) and tumor necrosis factor alpha (TNF-α), and enhanced transcription rates of interleukin 4 (IL-4) and interleukin 10 (IL-10). The spleen sections from the pNZ8124-OMPs-L. lactis and IRIBA group had less morphological damage associated with inflammation, infiltration of lymphocytes, and lesions to the spleen. The findings present a novel approach to utilizing the food-grade, non-pathogenic L. lactis as a protein cell factory to synthesize innovative immunological candidate OMPs. This approach offers a distinctive way to evaluate experimental medicinal items' practicality, safety, affordability, and long-term sustainability.

Keywords: Brucellosis infection; Live bacterial vectors; Mucosal vaccination; Protein delivery vehicles; Reverse vaccinology.

MeSH terms

  • Animals
  • Antibodies, Bacterial / blood
  • Antibodies, Bacterial / immunology
  • Bacterial Outer Membrane Proteins / genetics
  • Bacterial Outer Membrane Proteins / immunology
  • Brucella Vaccine* / administration & dosage
  • Brucella Vaccine* / genetics
  • Brucella Vaccine* / immunology
  • Brucella abortus* / immunology
  • Brucellosis* / immunology
  • Brucellosis* / prevention & control
  • Cytokines / metabolism
  • Epitopes / immunology
  • Female
  • Genetic Vectors
  • Immunoglobulin G / blood
  • Immunoglobulin G / immunology
  • Lactococcus lactis* / genetics
  • Lactococcus lactis* / immunology
  • Mice
  • Mice, Inbred BALB C*
  • Spleen / immunology

Substances

  • Brucella Vaccine
  • Bacterial Outer Membrane Proteins
  • Epitopes
  • Antibodies, Bacterial
  • Immunoglobulin G
  • Cytokines