Evaluation of ex vivo human immune response against candidate antigens for a visceral leishmaniasis vaccine.
People cured from visceral leishmaniasis (VL) develop protection mediated by Th1-type cellular responses against new infections. We evaluated cytokine responses against 6 defined candidate vaccine antigens in 15 cured VL subjects and 5 healthy endemic controls with no evidence of previous exposure to Leishmania parasites. Of the 6 cytokines examined, only interferon-gamma (IFN-gamma) differentiated cured VL patients from non-exposed individuals, with cured patients mounting a significantly higher IFN-gamma response to a crude parasite antigen preparation. Among candidate vaccine antigens tested, the largest number of cured subjects recognized cysteine proteinase B, leading to heightened IFN-gamma responses, followed by sterol 24-c-methyltransferase. These two antigens were the most immunogenic and protective antigens in a murine VL model, indicating a relationship between T cell recall responses of humans cured from VL and protective efficacy in an experimental model. Further studies may help prioritize antigens for clinical development of a subunit vaccine against VL.
Kumar
Rajiv
R
Department of Medicine, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India.
Goto
Yasuyuki
Y
Gidwani
Kamlesh
K
Cowgill
Karen D
KD
Sundar
Shyam
S
Reed
Steven G
SG
D000328:Adult; D000818:Animals; D000953:Antigens, Protozoan / Q000276:immunology*; D001681:Biological Assay; D016207:Cytokines / Q000096:biosynthesis / Q000097:blood; D004353:Drug Evaluation, Preclinical; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D007891:Leishmania / Q000276:immunology; D007898:Leishmaniasis, Visceral / Q000517:prevention & control*; D008213:Lymphocyte Activation / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016052:Protozoan Vaccines / Q000276:immunology*; D013154:Spleen / Q000166:cytology
D000953:Antigens, Protozoan; D016207:Cytokines; D016052:Protozoan Vaccines; D007371:Interferon-gamma