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.
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.
Resende
Daniela M
DM
Department of Biochemistry and Immunology, Federal University of Minas Gerais, Belo Horizonte, MG, 31270-901, Brazil.
Caetano
Bráulia C
BC
Dutra
Míriam S
MS
Penido
Marcus L O
ML
Abrantes
Christiane F
CF
Verly
Rodrigo M
RM
Resende
Jarbas M
JM
Piló-Veloso
Dorila
D
Rezende
Simone Aparecida
SA
Bruna-Romero
Oscar
O
Fernandes
Ana Paula
AP
Gazzinelli
Ricardo T
RT
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
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