title: Generation and evaluation of A2-expressing Lactococcus lactis live vaccines against Leishmania donovani in BALB/c mice.
abstract: Leishmaniasis is a parasitic disease affecting over 12 million individuals worldwide. As current treatments are insufficient, the development of an effective vaccine is a priority. This study generated and assessed the efficacy of Leishmania vaccines engineered from the non-colonizing, non-pathogenic Gram-positive bacterium Lactococcus lactis. A truncated, codon-optimized version of the A2 antigen from Leishmania donovani was engineered for expression in Lactococcus lactis in three different subcellular compartments: in the cytoplasm, secreted outside the cell or anchored to the cell wall. These three A2-expressing Lactococcus lactis strains were tested for their ability to generate A2-specific immune responses and as live vaccines against visceral Leishmania donovani infection in BALB/c mice. Subcutaneous immunization with live Lactococcus lactis expressing A2 anchored to the cell wall effectively induced high levels of antigen-specific serum antibodies. It was demonstrated that Lactococcus lactis-based vaccines are a feasible approach in the generation of live vaccines against leishmaniasis. The Lactococcus lactis strains generated in this study provide an excellent foundation for further studies on live bacterial vaccines against leishmaniasis and other pathogens.
authors.affiliation: Department of Microbiology and Immunology, McGill University, 3775 University Street, Montreal, QC H3A 2B4, Canada.
authors.forename: Karen K
authors.initials: KK
authors.lastname: Yam
authors.affiliation: Department of Microbiology and Immunology, McGill University, 3775 University Street, Montreal, QC H3A 2B4, Canada.
authors.forename: Felix
authors.initials: F
authors.lastname: Hugentobler
authors.affiliation: Department of Microbiology and Immunology, McGill University, 3775 University Street, Montreal, QC H3A 2B4, Canada.
authors.forename: Philippe
authors.initials: P
authors.lastname: Pouliot
authors.affiliation: Department of Microbiology and Immunology, McGill University, 3775 University Street, Montreal, QC H3A 2B4, Canada.
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Stern
authors.affiliation: Department of Microbiology and Immunology, McGill University, 3775 University Street, Montreal, QC H3A 2B4, Canada.
authors.forename: Jean-Daniel
authors.initials: JD
authors.lastname: Lalande
authors.affiliation: Department of Microbiology and Immunology, McGill University, 3775 University Street, Montreal, QC H3A 2B4, Canada.
authors.forename: Greg
authors.initials: G
authors.lastname: Matlashewski
authors.affiliation: Centre for the Study of Host Resistance, Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada.|Department of Microbiology and Immunology, McGill University, 3775 University Street, Montreal, QC H3A 2B4, Canada.
authors.forename: Martin
authors.initials: M
authors.lastname: Olivier
authors.affiliation: Department of Microbiology and Immunology, McGill University, 3775 University Street, Montreal, QC H3A 2B4, Canada.
authors.forename: Benoit
authors.initials: B
authors.lastname: Cousineau
mesh_terms: D000825:Animal Structures / Q000469:parasitology; D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood; D000953:Antigens, Protozoan / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D004195:Disease Models, Animal; D005260:Female; D005822:Genetic Vectors; D007279:Injections, Subcutaneous; D013294:Lactococcus lactis / Q000235:genetics*; D007893:Leishmania donovani / Q000276:immunology / Q000472:pathogenicity; D054332:Leishmaniasis Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D007898:Leishmaniasis, Visceral / Q000276:immunology / Q000517:prevention & control*; D051379:Mice; D008807:Mice, Inbred BALB C; D015800:Protozoan Proteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology
chemical_list: C107645:A2 protein, Leishmania donovani; D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D054332:Leishmaniasis Vaccines; D015800:Protozoan Proteins; D014614:Vaccines, Synthetic