title: BCG expressing LCR1 of Leishmania chagasi induces protective immunity in susceptible mice.
abstract: Cellular immune responses are required for protective immunity against Leishmania chagasi. Immunization strategies using live intracellular bacteria (e.g., bacille-Calmette Guerin strain of Mycobacterium bovis) expressing recombinant antigens can induce cellular immune responses to these antigens. Previous studies demonstrated that the L. chagasi antigen LCR1 stimulates IFN-gamma production from T cells of infected BALB/c mice, and immunization with recombinant LCR1 partially protects against L. chagasi infection. To determine whether live bacteria could enhance the immunization potential of LCR1, we engineered BCG expressing LCR1 (BCG-LCR1). Subcutaneous immunization with BCG-LCR1, but not with BCG containing plasmid only (BCG-pMV261), elicited better protective immunity against L. chagasi infection than LCR1 protein alone. BCG-LCR1 administered intraperitoneally did not protect. Splenocytes from mice immunized s.c. with either BCG-LCR1 or BCG-pMV261 and then infected with L. chagasi promastigotes had increased antigen-induced IFN-gamma and reduced IL-10 production compared to splenocytes of control mice. We propose that BCG-LCR1 promotes a Th1-type protective immune response, and it may be a useful component of a Leishmania vaccine.
authors.affiliation: Department of Internal Medicine, 300D EMRB, University of Iowa, Iowa City 52242, USA.
authors.forename: J A
authors.initials: JA
authors.lastname: Streit
authors.forename: T J
authors.initials: TJ
authors.lastname: Recker
authors.forename: J E
authors.initials: JE
authors.lastname: Donelson
authors.forename: M E
authors.initials: ME
authors.lastname: Wilson
mesh_terms: D000818:Animals; D000953:Antigens, Protozoan / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D001500:BCG Vaccine; D015153:Blotting, Western; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D018314:Leishmania infantum / Q000276:immunology*; D007898:Leishmaniasis, Visceral / Q000517:prevention & control*; D051379:Mice; D008807:Mice, Inbred BALB C; D016052:Protozoan Vaccines; D013154:Spleen / Q000166:cytology / Q000276:immunology; D014614:Vaccines, Synthetic
chemical_list: D000953:Antigens, Protozoan; D001500:BCG Vaccine; D016207:Cytokines; C093281:Lcr1 antigen; D016052:Protozoan Vaccines; D014614:Vaccines, Synthetic