title: Leishmanial antigens in liposomes promote protective immunity and provide immunotherapy against visceral leishmaniasis via polarized Th1 response.
abstract: Leishmaniasis affects 12 million people, and it is generally agreed that vaccination provides the best long-term strategy for its control. An ideal vaccine should be effective in both preventing and treating leishmaniasis. However, immunological correlates to predict vaccine efficacy and success of treatment in visceral leishmaniasis (VL) remain ill defined. Here, we correlated the vaccine efficacy of soluble leishmanial antigens (SLA) from Leishmania donovani promastigote membrane, entrapped in negative, neutral and positively charged liposomes with the elicited immune responses to predict vaccine success in experimental VL. Production of both IFN-gamma and IL-4 with a dominance of Th1 response following immunization was required for optimum success against L. donovani infection in BALB/c mice. The best vaccine formulation, SLA in positively charged liposomes, was then used for immunotherapy. This vaccine induced more than 90% elimination of parasites from both liver and spleen. The success of immunotherapy exhibited an immune modulation with surge in Th1 cytokines, IFN-gamma and IL-12 with extreme down regulation of disease promoting IL-4 and IL-10. These findings suggest that an immune modulation towards Th1 is effective for both successful vaccination and immunotherapy.
authors.affiliation: Infectious Diseases Division, Indian Institute of Chemical Biology, 4 Raja S.C. Mullick Road, Jadavpur, Kolkata 700032, India.
authors.forename: Sudipta
authors.initials: S
authors.lastname: Bhowmick
authors.forename: Rajesh
authors.initials: R
authors.lastname: Ravindran
authors.forename: Nahid
authors.initials: N
authors.lastname: Ali
mesh_terms: D000818:Animals; D000913:Antibodies, Protozoan / Q000032:analysis / Q000096:biosynthesis; D000953:Antigens, Protozoan / Q000008:administration & dosage / Q000276:immunology*; D049109:Cell Proliferation / Q000187:drug effects; D016207:Cytokines / Q000096:biosynthesis; D004339:Drug Compounding; D004563:Electrochemistry; D004591:Electrophoresis, Polyacrylamide Gel; D006868:Hydrolysis; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007167:Immunotherapy; D007371:Interferon-gamma / Q000096:biosynthesis; D018664:Interleukin-12 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D007893:Leishmania donovani / Q000276:immunology*; D007898:Leishmaniasis, Visceral / Q000276:immunology* / Q000517:prevention & control / Q000628:therapy*; D008081:Liposomes / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D046529:Microscopy, Electron, Transmission; D013154:Spleen / Q000166:cytology; D018417:Th1 Cells / Q000276:immunology*; D014357:Trypsin / Q000737:chemistry
chemical_list: D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D016207:Cytokines; D008081:Liposomes; D018664:Interleukin-12; D015847:Interleukin-4; D007371:Interferon-gamma; D014357:Trypsin