Leishmania donovani: identification of novel vaccine candidates using human reactive sera and cell lines.
Leishmaniasis is a complex of diseases caused by protozoan parasites belonging to the genus Leishmania. The development of specific resistance against re-infection after cure suggests that a vaccine approach is feasible. Various studies in humans and experimental animals strongly suggest that Th1 type of cell-mediated immune response is important for protection against the disease. A defined antigen that could elicit a specific T-cell-mediated immune response in the host would be an ideal candidate for the vaccine against this parasite. In order to select a candidate antigen, we established a screening system to identify the recombinant clone, expressing antigen having T-cell epitopes from a cDNA library. We screened the library using an established Leishmania specific cell line (LSCL) from a naive healthy human subject. The cell line with predominantly CD4+ cells behaved in a Leishmania specific manner. Fifty-two immuno-reactive clones were screened against the LSCL in vitro and we identified three cDNA clones expressing recombinant antigens that could induce proliferation of these cells to produce INFgamma. The protective efficacy of one of these recombinant proteins was investigated in a hamster model of experimental visceral leishmaniasis and showed protection against a virulent challenge. The identified antigens might be potential candidates for vaccine against Leishmania.
Arora
Sunil K
SK
Department of Immunopathology, Postgraduate Institute of Medical Education and Research, Chandigarh, India. skarora_in@yahoo.com
Pal
Nirbhai S
NS
Mujtaba
S
S
D000818:Animals; D000953:Antigens, Protozoan / Q000235:genetics / Q000276:immunology*; D015153:Blotting, Western; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000469:parasitology; D002460:Cell Line; D006224:Cricetinae; D018076:DNA, Complementary / Q000235:genetics; D016054:DNA, Protozoan / Q000235:genetics; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D015723:Gene Library; D006801:Humans; D007106:Immune Sera / Q000276:immunology*; D007111:Immunity, Cellular; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D007893:Leishmania donovani / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity; D007898:Leishmaniasis, Visceral / Q000517:prevention & control*; D008099:Liver / Q000033:anatomy & histology; D008297:Male; D008647:Mesocricetus; D016052:Protozoan Vaccines / Q000235:genetics / Q000276:immunology*; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology; D013154:Spleen / Q000033:anatomy & histology / Q000469:parasitology; D014774:Virulence
D000953:Antigens, Protozoan; D018076:DNA, Complementary; D016054:DNA, Protozoan; D007106:Immune Sera; D016052:Protozoan Vaccines; D011994:Recombinant Proteins; D007371:Interferon-gamma