A mixed Th1/Th2 response elicited by a liposomal formulation of Leishmania vaccine instructs Th1 responses and resistance to Leishmania donovani in susceptible BALB/c mice.
In this study, we have developed a vaccine with Leishmania donovani promastigote membrane antigens (leishmanial antigens (LAg)) encapsulated in a liposome carrier formulated with distearyol (DSPC, transition temperature (Tc) = 54 degrees C) derivative of l-alpha-phosphatidyl choline, for immunizing BALB/c mice against progressive visceral leishmaniasis. This formulation could limit hepatosplenomegaly to almost normal levels and conferred strong levels of protection in both liver and spleen against challenge infection. Immunization with liposomal LAg activated peritoneal macrophages for enhanced leishmanicidal activity in association with NO production, and induced antibody as well as T-cell mediated immune responses. Production of both IFN-gamma and IL-4 by splenic T cells, and serum IgG1 and IgG2a, suggest induction of a mixed Th1/Th2 response following immunization. Experimental challenge corresponded with elevated DTH, and mitogen and antigen specific cellular responses. Increased production of NO and IFN-gamma by spleen cells, and down regulation of IL-4, demonstrate that an initial stimulation of a mixed Th1/Th2 response by vaccination instructs Th1 responses and resistance against a progressive infection by L. donovani.
Infectious Diseases Group, Indian Institute of Chemical Biology, 4 Raja S.C. Mullick Road, Calcutta 700032, India.
Tuhina
T
Mazumdar
Khairul
K
Anam
Nahid
N
Ali
D000818:Animals; D000913:Antibodies, Protozoan / Q000032:analysis / Q000096:biosynthesis; D000953:Antigens, Protozoan / Q000276:immunology; D002455:Cell Division; D016207:Cytokines / Q000096:biosynthesis; D004337:Drug Carriers; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007114:Immunization; D007893:Leishmania donovani / Q000254:growth & development / Q000276:immunology*; D007898:Leishmaniasis, Visceral / Q000276:immunology* / Q000469:parasitology / Q000517:prevention & control*; D008081:Liposomes; D008099:Liver / Q000469:parasitology; D008264:Macrophages / Q000469:parasitology; D017737:Macrophages, Peritoneal / Q000276:immunology / Q000378:metabolism / Q000469:parasitology; D051379:Mice; D008807:Mice, Inbred BALB C; D009569:Nitric Oxide / Q000378:metabolism; D016052:Protozoan Vaccines / Q000008:administration & dosage / Q000276:immunology*; D013154:Spleen / Q000469:parasitology; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*
D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D016207:Cytokines; D004337:Drug Carriers; D008081:Liposomes; D016052:Protozoan Vaccines; D009569:Nitric Oxide