ABSTRACT
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.
Subject(s)
Leishmaniasis Vaccines/immunology , Leishmaniasis, Visceral/veterinary , Vaccines, Synthetic/microbiology , Adjuvants, Immunologic/pharmacology , Animals , Brazil , Dog Diseases/parasitology , Dog Diseases/prevention & control , Dogs , Humans , Leishmania donovani/immunology , Leishmaniasis, Visceral/prevention & control , Saponins/pharmacology , Vaccines, DNA/immunologyABSTRACT
The FML antigen of Leishmania donovani, in combination with either Riedel de Haën (R), QuilA, QS21 saponins, IL12 or BCG, was used in vaccination of an outbred murine model against visceral leishmaniasis (VL). Significant and specific increases in anti-FML IgG and IgM responses were detected for all adjuvants, and in anti-FML IgG1, IgG2a and IgG2b and delayed type of hypersensitivity to L. donovani lysate (DTH), only for all saponins and IL12. The QS21-FML and QuilA-FML groups achieved the highest IgG2a response. QuilA-FML developed the strongest DTH and QS21-FML animals showed the highest serum IFN-gamma concentrations. The reduction of parasitic load in the liver in response to each FML-vaccine formulation was: 52% (P<0.025) for BCG-FML, 73% (P<0.005) for R-FML, 93% (P<0.005) for QuilA-FML and 79.2% (P<0.025) for QS21-FML treated animals, respectively. Protection was specific for R-FML and QS21-FML while the QuilA saponin treatment itself induced 69% of LDU reduction. The FML-saponin vaccines promote significant, specific and strong protective effects against murine visceral leishmaniasis. BCG-FML induced minor and non-specific protection while IL12-FML, although enhancing the specific antibody and IDR response, failed to reduce the parasitic load of infected animals.
