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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adenoviridae / genetics
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Amino Acid Sequence
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Animals
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Antibodies, Protozoan / blood
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Antigens, Protozoan / genetics
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Antigens, Protozoan / immunology*
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CD4-Positive T-Lymphocytes / immunology
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CD8-Positive T-Lymphocytes / immunology*
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Cytotoxicity Tests, Immunologic
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Cytotoxicity, Immunologic*
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Epitope Mapping*
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Epitopes, B-Lymphocyte
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Epitopes, T-Lymphocyte
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Female
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Genetic Vectors
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Interferon-gamma / immunology*
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Leishmania donovani / genetics
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Leishmaniasis Vaccines / genetics
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Leishmaniasis Vaccines / immunology*
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Liver / parasitology
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Mice
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Mice, Inbred BALB C
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Models, Molecular
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Molecular Sequence Data
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Protozoan Proteins / genetics
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Protozoan Proteins / immunology*
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Spleen / parasitology
Substances
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A2 protein, Leishmania donovani
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Antibodies, Protozoan
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Antigens, Protozoan
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Epitopes, B-Lymphocyte
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Epitopes, T-Lymphocyte
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Leishmaniasis Vaccines
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Protozoan Proteins
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Interferon-gamma