title: Leishmania (Leishmania) amazonensis-induced cutaneous leishmaniasis in the primate Cebus apella: a model for vaccine trials.
abstract: A primate model of leishmaniasis was developed with the objective of future vaccine testing. Lesion development and immunological parameters were studied upon primary and secondary infections. Seven Cebus apella were injected subcutaneously with 2 x 10(6) Leishmania (Leishmania) amazonensis promastigotes. Erythematous nodules appeared 19-29 days p.i., which disappeared 100 days p.i. Four months later, six of the monkeys were challenged with the same inoculum; three of them developed erythematous nodules after 7 days p.i., with ulcer formation in two of these subjects. The lesions were short-lived and all were cured 40 days post challenge. Anti-Leishmania IgG antibodies were detected and they increased after the challenge infection. Leishmania antigen-induced lymphoproliferation was found 1 month post-primary infection, which coincided with IFN-gamma production and lesion development. It decreased to control levels afterwards, but at the time of the challenge dose, it was significantly above the initial level. After the challenge infection, it first increased then decreased sharply at 40 days post-challenge, coinciding with the healing of the lesion. It increased again to a higher level at 60 days post-challenge. Leishmania (Leishmania) amazonensis-infection in C. apella did not induce complete protection against a secondary infection with a homologous parasite although specific antibody production and lymphoproliferation with IFN-gamma production were observed. This fact indicates that vaccine has to be better than infection in the induction of protective immunity, and raises a question on in vitro parameters that should be considered as a counterpart of expected protection induced by vaccine candidate. In addition, we conclude that this is a useful primate model for the evaluation of candidate vaccines.
authors.affiliation: Seção de Parasitologia, Programa de Imunologia, Instituto Evandro Chagas, Fundação Nacional de Sáude, Ministério da Saúde-BR 316, Km 7 S/N, CEP 67.030-070, Ananindeua, PA, Brazil. lgarcez@amazon.com.br
authors.forename: Lourdes M
authors.initials: LM
authors.lastname: Garcez
authors.forename: Hiro
authors.initials: H
authors.lastname: Goto
authors.forename: Patrícia K
authors.initials: PK
authors.lastname: Ramos
authors.forename: Maria do Carmo
authors.initials: Mdo C
authors.lastname: Brigido
authors.forename: Patrick A F
authors.initials: PA
authors.lastname: Gomes
authors.forename: Railson A
authors.initials: RA
authors.lastname: Souza
authors.forename: Paula M
authors.initials: PM
authors.lastname: De Luca
authors.forename: Sergio C
authors.initials: SC
authors.lastname: Mendonça
authors.forename: José Augusto P C
authors.initials: JA
authors.lastname: Muniz
authors.forename: Jeffrey J
authors.initials: JJ
authors.lastname: Shaw
mesh_terms: D000818:Animals; D000913:Antibodies, Protozoan / Q000096:biosynthesis; D000953:Antigens, Protozoan / Q000276:immunology; D002428:Cebus; D002455:Cell Division / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D007074:Immunoglobulin G / Q000096:biosynthesis; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000096:biosynthesis; D007891:Leishmania / Q000276:immunology; D016773:Leishmaniasis, Cutaneous / Q000276:immunology* / Q000517:prevention & control; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D008992:Monkey Diseases / Q000276:immunology* / Q000517:prevention & control; D016052:Protozoan Vaccines
chemical_list: D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D007074:Immunoglobulin G; D016052:Protozoan Vaccines; D007371:Interferon-gamma