FML vaccine against canine visceral leishmaniasis: from second-generation to synthetic vaccine.

The Leishmania donovani glycoprotein fraction, known as FML, successfully underwent preclinical and clinical (Phase I-III) vaccine trials against canine visceral leishmaniasis (92-95% of protection and 76-80% of vaccine efficacy) when formulated with a QS21 saponin-containing adjuvant. It became the licensed Leishmune vaccine for canine prophylaxis in Brazil. The immune response raised by the vaccine is long lasting, immunotherapeutic and reduces dog infectivity blocking the transmission of the disease, as revealed by an in vivo assay. The preliminary epidemiological control data of vaccinated areas in Brazil indicate that, in spite of the still low vaccine coverage, there was a significant decrease in the incidence of the human and canine disease. A 36-kDa glycoprotein, in the FML complex, is the human marker of the disease, which was protective in mice as native recombinant protein or DNA vaccine. The DNA vaccine is now being tested against the canine disease. This review resumes the development of the second-generation FML-saponin-Leishmune vaccine, its adjuvant and of the NH36 DNA vaccine, toward the identification of its major epitopes that might be included in a possible future synthetic vaccine.

The FML (Fucose Mannose Ligand) of Leishmania donovani: a new tool in diagnosis, prognosis, transfusional control and vaccination against human kala-azar

The Fucose-Mannose Ligand (FML) of Leishmania donovani is a complex glycoproteic fraction. Its potential use as a tool for diagnosis of human visceral leishmaniasis was tested with human sera from Natal, Rio Grande do Norte, Brazil. The FML-ELISA test, showed 100 per cent sensitivity and 96 per cent specificity, identifying patients with overt kala-azar (p < 0.001, when compared to normal sera), and subjects with subclinical infection. More than 20 per cent apparently healthy subjects with positive reaction to FML developed overt kala-azar during the following 10 months. In the screening of human blood donnors, a prevalence of 5 per cent of sororeactive subjects was detected, attaining 17 per cent in a single day. The GP36 glycoprotein of FHL is specifically reconized by human kala-azar sera. The immunoprotective effect of FML on experimental L. donovani infection was tested in swiss albino mice. The protection scheemes included three weekly doses of FML, supplemented or not with saponin by the subcutaneous or intraperitoneal routes and challenge with 2 x 10(7) amastigotes of Leishmania donovani. An enhancement of 80.0 per cent in antibody response (p < 0.001) and reduction of 85.5 per cent parasite liver burden (p < 0.001) was detected in animals immunized with FML saponin, unrespectively of the immunization route.