title: Study of the safety, immunogenicity and efficacy of attenuated and killed Leishmania (Leishmania) major vaccines in a rhesus monkey (Macaca mulatta) model of the human disease.
abstract: We have compared the efficacy of two Leishmania (Leishmania) major vaccines, one genetically attenuated (DHFR-TS deficient organisms), the other inactivated [autoclaved promastigotes (ALM) with bacillus Calmete-Guérin (BCG)], in protecting rhesus macaques (Macaca mulatta) against infection with virulent L. (L.) major. Positive antigen-specific recall proliferative response was observed in vaccinees (79% in attenuated parasite-vaccinated monkeys, versus 75% in ALM-plus-BCG-vaccinated animals), although none of these animals exhibited either augmented in vitro gamma interferon (IFN-gamma) production or positive delayed-type hypersensitivity (DTH) response to the leishmanin skin test prior to the challenge. Following challenge, there were significant differences in blastogenic responses (p < 0.05) between attenuated-vaccinated monkeys and naïve controls. In both vaccinated groups very low levels of antibody were found before challenge, which increased after infective challenge. Protective immunity did not follow vaccination, in that monkeys exhibited skin lesion at the site of challenge in all the groups. The most striking result was the lack of pathogenicity of the attenuated parasite, which persisted in infected animals for up to three months, but were incapable of causing disease under the conditions employed. We concluded that both vaccine protocols used in this study are safe in primates, but require further improvement for vaccine application.
authors.affiliation: Departamento de Imunologia, Instituto Oswaldo Cruz-Fiocruz, Rio de Janeiro, Brasil.
authors.forename: V F
authors.initials: VF
authors.lastname: Amaral
authors.forename: A
authors.initials: A
authors.lastname: Teva
authors.forename: M P
authors.initials: MP
authors.lastname: Oliveira-Neto
authors.forename: A J
authors.initials: AJ
authors.lastname: Silva
authors.forename: M S
authors.initials: MS
authors.lastname: Pereira
authors.forename: E
authors.initials: E
authors.lastname: Cupolillo
authors.forename: R
authors.initials: R
authors.lastname: Porrozzi
authors.forename: S G
authors.initials: SG
authors.lastname: Coutinho
authors.forename: C
authors.initials: C
authors.lastname: Pirmez
authors.forename: S M
authors.initials: SM
authors.lastname: Beverley
authors.forename: G
authors.initials: G
authors.lastname: Grimaldi
mesh_terms: D000818:Animals; D000953:Antigens, Protozoan / Q000276:immunology; D001500:BCG Vaccine / Q000008:administration & dosage / Q000276:immunology; D004195:Disease Models, Animal; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007371:Interferon-gamma / Q000096:biosynthesis*; D018320:Leishmania major / Q000276:immunology*; D016773:Leishmaniasis, Cutaneous / Q000276:immunology / Q000517:prevention & control; D008253:Macaca mulatta; D016052:Protozoan Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D015164:Vaccines, Inactivated / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology
chemical_list: D000953:Antigens, Protozoan; D001500:BCG Vaccine; D016052:Protozoan Vaccines; D014613:Vaccines, Attenuated; D015164:Vaccines, Inactivated; D007371:Interferon-gamma