Experimental murine Leishmania donovani infection: immunoprotection by the fucose-mannose ligand (FML)

The fucose-mannose ligand (FML) of Leishmania donovani is a complex glycoprotein fraction present in pro- and amastigotes, that interferes with parasite-macrophage interactions in vitro. In the present study, we have tested the potential immunoprotective effect of FML on L. donovani infection in inbred female BALB/c mice. The protection schemes included three weekly intraperitoneal administrations of FML, supplemented or not with saponin. Mice were challenged by intravenous injections of 2 x 10(7) amastigotes of Leishmania donovani (LD-1S/MHOM/SD/00-strain 1S) obtained from CB hamsters' infected spleens. After 15 days of infection, we monitored the splenocyte proliferative response to FML in vitro by ELISA for specific antibody response, and by parasite quantification as "Leishman-Donovan Units" in liver. A significant (P < 0.001) protective effect of FML with saponin, but not of FML or saponin alone, was shown by the reduction of parasite burden in liver and by the enhancement of splenocyte proliferation. The antibody response, very low at 15 days of infection in both untreated and control animals, showed a pronounced increase (P < 0.001) in animals sensitized with FML/saponin. Taken together, our results represent a 79.1 and 89.1% increase in specific proliferative and antibody responses, respectively, and an 84.4% protection in reduction of parasite liver burden. The protective potential was specifically due to FML (P < 0.001). Under the present conditions, no toxic or nonspecific effect could be attributed to saponin. A detailed study of the molecular events related to vaccination against murine visceral leishmaniasis with total and fractionated FML is currently underway.