Leishmaniasis vaccine candidates for development: a global overview.

A vaccine against different forms of leishmaniasis should be feasible considering the wealth of information on genetics and biology of the parasite, clinical and experimental immunology of leishmaniasis, and the availability of vaccines that can protect experimental animals against challenge with different Leishmania species. However, there is no vaccine against any form of leishmaniasis for general human use. One major factor is the lack of a conceived market for human leishmaniasis vaccines. Hence pharmaceutical industries involved in vaccine development are not interested in investing millions of dollars and a decade that is required for developing a new vaccine. Besides, leishmaniasis is a local/regional problem and not a global one. According to the estimates of the World Health Organization, 90 per cent of visceral leishmaniasis occurs in five countries (Bangladesh, Brazil, India, Nepal and Sudan). Those in need are amongst the poorest people in these countries. It should therefore be the objectives of these countries to develop a vaccine. Fortunately, both Brazil and India have designated the control of visceral leishmaniasis as a top priority for their respective Ministries of Health. The purpose of this review is to present only the vaccines in use and those in development for use in dogs or humans. This is not an exhaustive review of vaccine discovery or the principles of clinical immunology underlying vaccine development.

The FML vaccine (fucose-mannose ligand) protects hamsters from experimental kala-azar

Visceral leishmaniais or kala-azar, is a chronic and frequently lethal disease, caused by Leishmania donovani. Clinical signs include malaise, hepatosplenomegaly, hypergammaglobulinemia, fever, cachexia and progressive suppresion of the cellular immune response. Only few studies on prophylactic immunization against this disease have been understaken, mostly with crude antigens, and no vaccine against kala-azar is yet available. In previous studies, we have isolated the Fucose-Mannose Ligand (FML) of L. donovani that strongly and specifically inhibits the in vitro infection of macrophages by promastigotes and amastigotes. The FML behaves as a pontent immunogen for rabbits and mice, and is specifically recognized by kala-azar patient sera. The protective pontential of FML on kala-azar was now analyzed in the CB-hamster model. We studied the efect of three intraperitoneal weekly doses of FML (100 mg) in saponin (100 mg), folowed by an intracardiac injection of 107 amastigotes. Saponin- and saline-treated controls were also included. Protection was highly significant regarding the enhancement of anti-FML antibodies titers, the splenocyte proliferative response, and the intradermal delayed hypersensitivity reaction to antigen, as well as the decrease of the parasite burden in spleen and of splenomegaly. Protection to kala-azar was due to specific FML antigenic properties, since the results obtained by saponin alone were significantly different. We conclude that the use of FML and saponin as a vaccine reduced the disease impact and retarded its onset.