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

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.

Leishmania donovani Nucleoside Hydrolase Terminal Domains in Cross-Protective Immunotherapy Against Leishmania amazonensis Murine Infection

“…F3 is then the target of the anti- Leishmania cross-specific humoral response of mice (48), and the antibody target of humans and dogs with VL (49) and of dogs vaccinated with Leishmune ® (17). Since the antibodies generated by the Leishmune ® vaccine in dogs reacted mostly with the F3 epitopes (48) and block the transmission of VL in the insect vector (18, 19), the identification of these cross-reactive immunogenic sequences in F3 might also help in blocking the transmission of CL.…”

“…Consequently, we believe that the search for cross-protective antigens is mandatory. Recently, we developed the first licensed second generation vaccine against canine VL leishmaniasis (Leishmune ® ), which contains the fucose–mannose ligand (FML) antigen of L. donovani in formulation with saponin (16–19), is a transmission blocking vaccine (18, 19) and has already determined a reduction in the incidence of the human and canine disease in Brazilian endemic areas (20). Prophylactic vaccination of dogs with Leishmune ® promoted increases in the production of NO, IgG2 antibodies against FML and L. chagasi , intradermal reactions and proportions of CD8 + lymphocytes, which secrete more IFN-γ than IL-4 (21, 22) expressing a selective pro-inflammatory pattern (IFN-γ/NO) (23).…”

Vaccine candidates for leishmaniasis: A review

“…Various studies have been carried out in dogs using FML antigen in combination with saponin as an adjuvant and encouraging results have been observed in almost all cases [161][162][163][164][165][166]. Vaccination with FML antigen conferred effective protection with increased level of IgG2a and 79-100% delayed type hypersensitivity (DTH) response in experimentally infected [163] and naturally exposed dogs [161].…”

“…Its gp36 glycoprotein, identified as a main component of FML, was specifically recognized by sera of rabbit [131] and used as a marker in human patients [155,166]. The use of GP36 in immunization also induced a strong and specific protection against L. donovani infection [160].…”

F1 Domain of the Leishmania (Leishmania) donovani Nucleoside Hydrolase Promotes a Th1 Response in Leishmania (Leishmania) infantum Cured Patients and in Asymptomatic Individuals Living in an Endemic Area of Leishmaniasis

“…In Europe, there are two veterinary vaccines, one composed of the 54 kDa native excreted/secreted protein (Canileish) (6) and the other a chimera recombinant multiprotein protein Q, which contains the acidic ribosomal proteins Lip2a, Lip2b, P0, and histone H2A (7) (Latifend). In Brazil, the FML glycoprotein extract of L. (L.) donovani (Leishmune ® ) (8–11) was the first commercial vaccine in the world licensed in 2003. After that, the A2 recombinant protein of L. (L.) infantum chagasi (Leish-Tec ® ) (12) was also licensed in Brazil, in 2007 (13).…”