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

Vaccine. 2008 Aug 18;26(35):4585-93. doi: 10.1016/j.vaccine.2008.05.091. Epub 2008 Jun 25.

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

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / genetics
  • Amino Acid Sequence
  • Animals
  • Antibodies, Protozoan / blood
  • Antigens, Protozoan / genetics
  • Antigens, Protozoan / immunology*
  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / immunology*
  • Cytotoxicity Tests, Immunologic
  • Cytotoxicity, Immunologic*
  • Epitope Mapping*
  • Epitopes, B-Lymphocyte
  • Epitopes, T-Lymphocyte
  • Female
  • Genetic Vectors
  • Interferon-gamma / immunology*
  • Leishmania donovani / genetics
  • Leishmaniasis Vaccines / genetics
  • Leishmaniasis Vaccines / immunology*
  • Liver / parasitology
  • Mice
  • Mice, Inbred BALB C
  • Models, Molecular
  • Molecular Sequence Data
  • Protozoan Proteins / genetics
  • Protozoan Proteins / immunology*
  • Spleen / parasitology

Substances

  • A2 protein, Leishmania donovani
  • Antibodies, Protozoan
  • Antigens, Protozoan
  • Epitopes, B-Lymphocyte
  • Epitopes, T-Lymphocyte
  • Leishmaniasis Vaccines
  • Protozoan Proteins
  • Interferon-gamma