title: 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.
authors.affiliation: Instituto de Microbiologia, CCS, UFRJ, Avda Carlos Chagas 373, Caixa Postal 68040, 21941-590 Cidade Universitária, Ilha do Fundão, Rio de Janeiro, Brazil. immgcpa@micro.ufrj.br
authors.forename: Clarisa B
authors.initials: CB
authors.lastname: Palatnik-de-Sousa
authors.forename: André de Figueiredo
authors.initials: Ade F
authors.lastname: Barbosa
authors.forename: Sandra Maria
authors.initials: SM
authors.lastname: Oliveira
authors.forename: Dirlei
authors.initials: D
authors.lastname: Nico
authors.forename: Robson Ronney
authors.initials: RR
authors.lastname: Bernardo
authors.forename: Wania R
authors.initials: WR
authors.lastname: Santos
authors.forename: Mauricio M
authors.initials: MM
authors.lastname: Rodrigues
authors.forename: Irene
authors.initials: I
authors.lastname: Soares
authors.forename: Gulnara P
authors.initials: GP
authors.lastname: Borja-Cabrera
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D001938:Brazil; D004283:Dog Diseases / Q000469:parasitology / Q000517:prevention & control; D004285:Dogs; D006801:Humans; D007893:Leishmania donovani / Q000276:immunology; D054332:Leishmaniasis Vaccines / Q000276:immunology*; D007898:Leishmaniasis, Visceral / Q000517:prevention & control / Q000662:veterinary*; D012503:Saponins / Q000494:pharmacology; D019444:Vaccines, DNA / Q000276:immunology; D014614:Vaccines, Synthetic / Q000382:microbiology*
chemical_list: D000276:Adjuvants, Immunologic; D054332:Leishmaniasis Vaccines; D012503:Saponins; D019444:Vaccines, DNA; D014614:Vaccines, Synthetic; C078785:saponin QA-21V1