Making an anti-amastigote vaccine for visceral leishmaniasis: rational, update and perspectives.
Visceral leishmaniasis is a major health problem in Latina America, as well as the Mediterranean region of Europe and Asia. We aimed to develop a vaccine against visceral leishmaniasis targeting the intracellular amastigotes, which is the parasite stage that persists throughout infections with Leishmania parasites. With this in mind, we identified an amastigote specific antigen (A2) that contains an immunogenic epitope for CD4+ T helper (Th) cells and multiple repetitive units encoding CD8+ cytotoxic T lymphocyte (CTL) epitopes. Vaccine formulations containing the recombinant A2 associated with saponin, alum and IL-12 or expressed by attenuated adenovirus were shown to be protective in mice, dogs and nonhuman-primates. We are currently identifying novel amastigote specific immunogenic proteins that could be aggregated to A2 to further improve the level of vaccine-induced cell-mediated immunity and protection against visceral leishmaniasis.
Faculdade de Farmácia, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil. anapaula.fernandes@pq.cnpq.br
Ana Paula
AP
Fernandes
Eduardo Antonio Ferraz
EA
Coelho
George Luiz Lins
GL
Machado-Coelho
Gabriel
G
Grimaldi
Ricardo Tostes
RT
Gazzinelli
D000818:Animals; D000913:Antibodies, Protozoan / Q000276:immunology; D000953:Antigens, Protozoan / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D004285:Dogs; D006801:Humans; D018664:Interleukin-12 / Q000276:immunology; D007893:Leishmania donovani / Q000276:immunology* / Q000472:pathogenicity; D054332:Leishmaniasis Vaccines / Q000276:immunology*; D007898:Leishmaniasis, Visceral / Q000276:immunology* / Q000517:prevention & control*; D008253:Macaca mulatta; D051379:Mice; D015800:Protozoan Proteins / Q000276:immunology
D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D054332:Leishmaniasis Vaccines; D015800:Protozoan Proteins; D018664:Interleukin-12