Leishmania donovani triose phosphate isomerase: a potential vaccine target against visceral leishmaniasis.
Visceral leishmaniasis (VL) is one of the most important parasitic diseases with approximately 350 million people at risk. Due to the non availability of an ideal drug, development of a safe, effective, and affordable vaccine could be a solution for control and prevention of this disease. In this study, a potential Th1 stimulatory protein- Triose phosphate isomerase (TPI), a glycolytic enzyme, identified through proteomics from a fraction of Leishmania donovani soluble antigen ranging from 89.9-97.1 kDa, was assessed for its potential as a suitable vaccine candidate. The protein- L. donovani TPI (LdTPI) was cloned, expressed and purified which exhibited the homology of 99% with L. infantum TPI. The rLdTPI was further evaluated for its immunogenicity by lymphoproliferative response (LTT), nitric oxide (NO) production and estimation of cytokines in cured Leishmania patients/hamster. It elicited strong LTT response in cured patients as well as NO production in cured hamsters and stimulated remarkable Th1-type cellular responses including IFN-ã and IL-12 with extremely lower level of IL-10 in Leishmania-infected cured/exposed patients PBMCs in vitro. Vaccination with LdTPI-DNA construct protected naive golden hamsters from virulent L. donovani challenge unambiguously (∼90%). The vaccinated hamsters demonstrated a surge in IFN-ã, TNF-á and IL-12 levels but extreme down-regulation of IL-10 and IL-4 along with profound delayed type hypersensitivity and increased levels of Leishmania-specific IgG2 antibody. Thus, the results are suggestive of the protein having the potential of a strong candidate vaccine.
Division of Parasitology, Central Drug Research Institute, Lucknow, India.
Pramod K
PK
Kushawaha
Reema
R
Gupta
Chandra Dev Pati
CD
Tripathi
Prashant
P
Khare
Anil Kumar
AK
Jaiswal
Shyam
S
Sundar
Anuradha
A
Dube
D000818:Animals; D002460:Cell Line; D049109:Cell Proliferation; D003001:Cloning, Molecular; D006224:Cricetinae; D016207:Cytokines / Q000378:metabolism; D005260:Female; D006019:Glycolysis; D006801:Humans; D007074:Immunoglobulin G / Q000737:chemistry; D016898:Interferon-alpha / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D007893:Leishmania donovani / Q000201:enzymology*; D007898:Leishmaniasis, Visceral / Q000469:parasitology* / Q000517:prevention & control*; D007963:Leukocytes, Mononuclear / Q000201:enzymology; D008214:Lymphocytes / Q000166:cytology / Q000469:parasitology; D008297:Male; D008647:Mesocricetus; D009569:Nitric Oxide / Q000737:chemistry; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000378:metabolism; D014305:Triose-Phosphate Isomerase / Q000737:chemistry* / Q000276:immunology
D016207:Cytokines; D007074:Immunoglobulin G; D016898:Interferon-alpha; D012333:RNA, Messenger; D018664:Interleukin-12; D015847:Interleukin-4; D009569:Nitric Oxide; D014305:Triose-Phosphate Isomerase