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.

Keywords::

• canine visceral leishmaniasis
• CP05 saponin
• DNA vaccine
• FML antigen
• human visceral leishmaniasis
• Leishmania chagasi
• Leishmania donovani
• nucleoside hydrolase
• QS21 saponin
• second-generation vaccine
• transmission-blocking vaccine

Acknowledgements

We are grateful to I Amorim, E Freitas, MN Melo, MSM Michalick, ESDias and A Costa-Val for the great effort made to obtain the xenodiagnostic results and to I Silva-Antunes and A Aguiar Morgado from the Center for Zoonoses Control, Araçatuba, São Paulo, Brazil, for the official epidemiological data. The authors are gratefull to David Straker for English review.

Financial & competing interests disclosure

This work was financially supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) (Edital Milênio 420067/2005, Edital Universal 473830/2007-8 and productitivity fellowship 301215/2007-3), Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ-PRONEX, CNE fellowship E-26/152824/2006, Edital Pensa Rio E-26/110305/2007 and Edital FAPERJ-INFRA E-26/110132) and Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP 2006/02832-0). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.