BCG expressing LCR1 of Leishmania chagasi induces protective immunity in susceptible mice.
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.
Streit
J A
JA
Department of Internal Medicine, 300D EMRB, University of Iowa, Iowa City 52242, USA.
Recker
T J
TJ
Donelson
J E
JE
Wilson
M E
ME
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
D000953:Antigens, Protozoan; D001500:BCG Vaccine; D016207:Cytokines; C093281:Lcr1 antigen; D016052:Protozoan Vaccines; D014614:Vaccines, Synthetic