title: Epitope mapping and protective immunity elicited by adenovirus expressing the Leishmania amastigote specific A2 antigen: correlation with IFN-gamma and cytolytic activity by CD8+ T cells.
abstract: A2 was identified as an amastigote virulence factor of Leishmania (Leishmania) donovani and as a candidate antigen for vaccine development against visceral leishmaniasis. Here, predicted hydrophilic, class I and II MHC-binding synthetic peptides were used to define epitopes recognized by A2-specific antibodies, CD8+ T and CD4+ T cells, respectively. Immunization of BALB/c mice with adenovirus expressing A2 (AdA2) resulted in low antibody response, contrasting with high levels of IFN-gamma producing CD4+ T and CD8+ T cells specific for A2. Further, A2-specific CD8+ T cells from immunized mice were capable of lysing sensitized target cells in vivo. Finally, we demonstrated an association of A2-specific T cell responses and reduced parasitism in both liver and spleen from mice immunized with AdA2 and challenged with L. (L.) chagasi.
authors.affiliation: Department of Biochemistry and Immunology, Federal University of Minas Gerais, Belo Horizonte, MG, 31270-901, Brazil.
authors.forename: Daniela M
authors.initials: DM
authors.lastname: Resende
authors.forename: Bráulia C
authors.initials: BC
authors.lastname: Caetano
authors.forename: Míriam S
authors.initials: MS
authors.lastname: Dutra
authors.forename: Marcus L O
authors.initials: ML
authors.lastname: Penido
authors.forename: Christiane F
authors.initials: CF
authors.lastname: Abrantes
authors.forename: Rodrigo M
authors.initials: RM
authors.lastname: Verly
authors.forename: Jarbas M
authors.initials: JM
authors.lastname: Resende
authors.forename: Dorila
authors.initials: D
authors.lastname: Piló-Veloso
authors.forename: Simone Aparecida
authors.initials: SA
authors.lastname: Rezende
authors.forename: Oscar
authors.initials: O
authors.lastname: Bruna-Romero
authors.forename: Ana Paula
authors.initials: AP
authors.lastname: Fernandes
authors.forename: Ricardo T
authors.initials: RT
authors.lastname: Gazzinelli
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000595:Amino Acid Sequence; D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood; D000953:Antigens, Protozoan / Q000235:genetics / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003601:Cytotoxicity Tests, Immunologic; D003602:Cytotoxicity, Immunologic; D018604:Epitope Mapping; D018985:Epitopes, B-Lymphocyte; D018984:Epitopes, T-Lymphocyte; D005260:Female; D005822:Genetic Vectors; D007371:Interferon-gamma / Q000276:immunology*; D007893:Leishmania donovani / Q000235:genetics; D054332:Leishmaniasis Vaccines / Q000235:genetics / Q000276:immunology*; D008099:Liver / Q000469:parasitology; D051379:Mice; D008807:Mice, Inbred BALB C; D008958:Models, Molecular; D008969:Molecular Sequence Data; D015800:Protozoan Proteins / Q000235:genetics / Q000276:immunology*; D013154:Spleen / Q000469:parasitology
chemical_list: C107645:A2 protein, Leishmania donovani; D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D018985:Epitopes, B-Lymphocyte; D018984:Epitopes, T-Lymphocyte; D054332:Leishmaniasis Vaccines; D015800:Protozoan Proteins; D007371:Interferon-gamma