The objective of the proposed research is to characterize the immunoprotective and immunodepressive properties of Leishmania donavani exometabolite which the applicant has demonstrated to be a complex lipid (glycopeptidophosphosphingolipid (GPPSL)). To facilitate these studies the physico-chemical characterization will be continued to establish the molecular weight, empirical formula and specific molecular residues with their sequence and bonding. Preliminary studies demonstrated that mice vaccinated subcutaneously with GPPSL incorporated into stable liposomes mixed with lipid adjuvant developed strong delayed hypersensitivity responses upon challenge with the homologous antigen preparation and these mice were highly resistant to a virulent homologous challenge infection. On the other hand, nonspecific immunodepression was induced after inoculation intravenously of GPPSL incorporated into unstable liposomes. The immunoprotective effect of L. donavani GPPSL will be studied by (1) characterizing the nature of the protective immune response; (2) determining the most effective liposomal -GPPSL-adjuvant formulation; (3) establishing the stability of the protective immune response with time; (4) studying the effect of vaccine on development of granulomatous lesions in the host; (5) establishing whether hamsters can be effectively protected against terminal disease by the vaccine. The immunodepressive qualities will be studied by determining the effect of free GPPSL on induction and elicitation of immunity to L. donovani in the intact vertebrate host and on isolated cell preparations. It is proposed also to determine if the immunoprotective and immunodepressive properties of GPPSL are shared by smiliar material released by another species, Leishmania tropica. The ultimate goal is to establish which part of the GPPSL molecule is responsible for the diverse immunological responses, isolate the immunoprotective fragment and construct a synthetic immunogen which is highly immunogenic but free immunodepressive qualities.
