title: Immunogenicity in dogs of three recombinant antigens (TSA, LeIF and LmSTI1) potential vaccine candidates for canine visceral leishmaniasis.
abstract: Control of canine visceral leishmaniasis (VL) remains a difficult and serious problem mostly because there is no reliable and effective vaccine available to prevent this disease. A mixture of three recombinant leishmanial antigens (TSA, LeIF and LmSTI1) encoded by three genes highly conserved in the Leishmania genus have been shown to induce excellent protection against infection in both murine and simian models of cutaneous leishmaniasis. A human clinical trial with these antigens is currently underway. Because of the high degree of conservation, these antigens might be useful vaccine candidates for VL as well. In the present study, using the dog model of the visceral disease, we evaluated the immunogenicity of these three antigens formulated with two different adjuvants, MPL-SE and AdjuPrime. The results were compared with a whole parasite vaccine formulated with BCG as the adjuvant. In order to investigate if sensitization with the recombinant antigens would result in recognition of the corresponding native parasite antigens upon infection, the animals were exposed for four weeks after the termination of the immunization protocol with the recombinant antigens to a low number of L. chagasi promastigotes, an etiological agent of VL. Immune response was evaluated by quantitative ELISA in the animal sera before and after exposure to the viable parasites. Both antigen specific IgG1 and IgG2 antibody levels were measured. Immunization of dogs with the recombinant antigens formulated in either MPL-SE or AdjuPrime resulted in high antibody levels particularly to LmSTI1. In addition, this immunization although to low levels, resulted in the development of antibody response to the whole parasite lysate. Importantly, experimental exposure with low numbers of culture forms of L. chagasi promastigotes caused a clear boost in the immune response to both the recombinant antigens and the corresponding native molecules. The boost response was predominantly of the IgG2 isotype in animals primed with the recombinant antigens plus MPL-SE. In contrast, animals primed with the recombinant antigens formulated in AdjuPrime as well as animals vaccinated with crude antigen preparation responded with mixed IgG1/IgG2 isotypes. These results point to the possible use of this antigen cocktail formulated with the adjuvant MPL-SE in efficacy field trials against canine VL.
authors.affiliation: Laboratório de Leishmanioses e Vacinas, Departamento de Parasitologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais (UFMG), CEP 31270-901, Belo Horizonte, MG, Brazil. mtmrtf@gwumc.edu
authors.forename: Ricardo Toshio
authors.initials: RT
authors.lastname: Fujiwara
authors.forename: André Macedo
authors.initials: AM
authors.lastname: Vale
authors.forename: João Carlos
authors.initials: JC
authors.lastname: França da Silva
authors.forename: Roberto Teodoro
authors.initials: RT
authors.lastname: da Costa
authors.forename: Josiane da Silva
authors.initials: Jda S
authors.lastname: Quetz
authors.forename: Olindo Assis
authors.initials: OA
authors.lastname: Martins Filho
authors.forename: Alexandre Barbosa
authors.initials: AB
authors.lastname: Reis
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Corrêa Oliveira
authors.forename: George Lins
authors.initials: GL
authors.lastname: Machado-Coelho
authors.forename: Lilian Lacerda
authors.initials: LL
authors.lastname: Bueno
authors.forename: Jeffrey Michael
authors.initials: JM
authors.lastname: Bethony
authors.forename: Glen
authors.initials: G
authors.lastname: Frank
authors.forename: Evaldo
authors.initials: E
authors.lastname: Nascimento
authors.forename: Odair
authors.initials: O
authors.lastname: Genaro
authors.forename: Wilson
authors.initials: W
authors.lastname: Mayrink
authors.forename: Steven
authors.initials: S
authors.lastname: Reed
authors.forename: Antonio
authors.initials: A
authors.lastname: Campos-Neto
mesh_terms: D000818:Animals; D000913:Antibodies, Protozoan / Q000096:biosynthesis; D000953:Antigens, Protozoan / Q000276:immunology*; D004283:Dog Diseases / Q000276:immunology* / Q000469:parasitology; D004285:Dogs; D007898:Leishmaniasis, Visceral / Q000276:immunology / Q000662:veterinary*; D016052:Protozoan Vaccines / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000276:immunology
chemical_list: D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D016052:Protozoan Vaccines; D014614:Vaccines, Synthetic