Development of the FML-Vaccine Against Canine Visceral Leishmaniasis: From the Second-Generation to the Synthetic Vaccine
C.B. Palatnik de Sousa
Senior Professor of Microbiology Institute for Microbiology "Paulo de Góes" Federal University of Rio de Janeiro
The Leishmania donovani glycoprotein fraction named FML, successfully underwent preclinical and clinical 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 disclosed by an in vivo assay. In spite of the still low vaccine coverage, there was a significant decrease in the incidence of the human and canine disease related to the Leishmune® vaccination which does not interfere with the serological control campaign (110,000 dogs). Only 1.3% of positivity (76 among 5,860) was detected among Leishmune® uninfected vaccinees. In Araçatuba, a 25% of decline was seen in CVL with a 61% decline in human cases, indicating the additive effect of Leishmune® vaccination of the healthy dogs, on regular dog culling (2004-2006). In Belo Horizonte, the districts showing a decrease of human incidence showed the highest dog vaccination percents and the lowest dog incidence. Conversely, much lower proportions of dogs were vaccinated in the districts that exhibited very increased canine and human incidence. The decrease of incidence is correlated to the increase of the number of vaccinated dogs, confirming the additive control effect of Leishmune® vaccination over dog culling. A 36 kDa glycoprotein is, in the FML complex, the human marker of the disease which was protective in mice, as native, recombinant protein or DNA vaccine. The DNA-vaccine has shown to be prophylactic and therapeutic against dog infection. We will describe the development of the FML-saponin-Leishmune® prophylactic and immunotherapeutic vaccine, its adjuvant, the DNA vaccine, and the identification of its major epitopes to be included in a possible future synthetic vaccine.