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* Division of Parasitology and
Division of Molecular & Structural Biology, Central Drug Research Institute, Lucknow, India
Leishmania produce several types of mucin-like glycoproteins called proteophosphoglycans (PPGs) which exist as secretory as well as surface-bound forms in both promastigotes and amastigotes. The structure and function of PPGs have been reported to be species and stage specific as in the case of Leishmania major and Leishmania mexicana; there has been no such information available for Leishmania donovani. We have recently demonstrated that PPG is differentially expressed in sodium stibogluconate-sensitive and -resistant clinical isolates of L. donovani. To further elucidate the structure and function of the ppg gene of L. donovani, a partial sequence of its N-terminal domain of 1.6 kb containing the majority of antigenic determinants, was successfully cloned and expressed in prokaryotic as well as mammalian cells. We further evaluated the DNA-encoding N-terminal domain of the ppg gene as a vaccine in golden hamsters (Mesocricetus auratus) against the L. donovani challenge. The prophylactic efficacy to the tune of 
80% was observed in vaccinated hamsters and all of them could survive beyond 6 mo after challenge. The efficacy was supported by a surge in inducible NO synthase, IFN-
, TNF-
, and IL-12 mRNA levels along with extreme down-regulation of TGF-β, IL-4, and IL-10. A rise in the level of Leishmania-specific IgG2 was also observed which was indicative of enhanced cellular immune response. The results suggest the N-terminal domain of L. donovani ppg as a potential DNA vaccine against visceral leishmaniasis.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by the Department of Science and Technology New Delhi and Council for Scientific and Industrial Research Project-Suprainstitutional Network Project No. 0026. M.S., R.G., S.K., P.M., and P.K.K. are the recipients of Council for Scientific and Industrial Research and University Grants Commission fellowships.
2 Address correspondence and reprint requests to Dr. Anuradha Dube, Division of Parasitology, Central Drug Research Institute, Post Box 173, Lucknow-226 001, India. E-mail addresses: anuradha_dube{at}hotmail.com or anuradha_dube{at}rediffmail.com
3 Abbreviations used in this paper: PG, phosphoglycan; PPG, proteophosphoglycan; VL, visceral leishmaniasis; SLD, soluble Leishmania donovani; iNOS, inducible NO synthase; DTH, delayed-type hypersensitivity; p.c., postchallenge; IPTG, isopropyl-β-D-thiogalactopyranoside; WCL, whole cell lysate; PI, percentage of inhibition; SI, stimulation index; CT, cycle threshold; CMI, cell-mediated immunity; LTT, lymphocyte transformation test.
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