Abstract

The purpose of this proposal is to continue and extend the previous work supported by grant AI-23004, to delineate both the antigens and mechanisms involved in protective immunity for leishmaniasis. In addition, the proposal is to investigate biochemical differences responsible for the survival of the parasite in each of the life cycle stages (promastigote- amastigote).
The specific aims are: 1. Identification and evaluation (in vivo) of antigens protective against an infection with Leishmania sp.. 2. Elucidation of the effector mechanisms involved in a protective immune response against leishmaniasis. 3. Development of methods/strains for the axenic culture of Leishmania amastigotes. 4. Molecular biological, biochemical, and biological characterization of stage-specific antigens (promastigote and amastigote) of Leishmania. 5. Studies of the M-2 Gene Family. 6. Molecular cloning of stage-specific and protective antigens. 7. Development of a reliable specific serological diagnostic assay for visceral leishmaniasis.
The aims of this proposal are essentially those of the original proposal; however, the methodology and approaches being taken have been expended based on the progress that has occurred during the past two years.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI023004-07
Application #
3134810
Study Section
Tropical Medicine and Parasitology Study Section (TMP)
Project Start
1985-06-01
Project End
1993-05-31
Budget Start
1991-06-01
Budget End
1992-05-31
Support Year
7
Fiscal Year
1991
Total Cost
Indirect Cost

  Institution

Name
Yale University
Department
Type
Schools of Medicine
DUNS #
082359691
City
New Haven
State
CT
Country
United States
Zip Code
06520

  Publications

Kima, P E; Ruddle, N H; McMahon-Pratt, D (1997) Presentation via the class I pathway by Leishmania amazonensis-infected macrophages of an endogenous leishmanial antigen to CD8+ T cells. J Immunol 159:1828-34
Soong, L; Xu, J C; Grewal, I S et al. (1996) Disruption of CD40-CD40 ligand interactions results in an enhanced susceptibility to Leishmania amazonensis infection. Immunity 4:263-73
Amaral, V F; Ransatto, V A; Conceicao-Silva, F et al. (1996) Leishmania amazonensis: the Asian rhesus macaques (Macaca mulatta) as an experimental model for study of cutaneous leishmaniasis. Exp Parasitol 82:34-44
Kima, P E; Soong, L; Chicharro, C et al. (1996) Leishmania-infected macrophages sequester endogenously synthesized parasite antigens from presentation to CD4+ T cells. Eur J Immunol 26:3163-9
McMahon-Pratt, D; Rodriguez, D; Rodriguez, J R et al. (1993) Recombinant vaccinia viruses expressing GP46/M-2 protect against Leishmania infection. Infect Immun 61:3351-9
Grimaldi Junior, G; Kreutzer, R D; Hashiguchi, Y et al. (1992) Description of Leishmania equatorensis sp. n (Kinetoplastida: Trypanosomatidae), a new parasite infecting arboreal mammals in Ecuador. Mem Inst Oswaldo Cruz 87:221-8
Bonfante-Garrido, R; Melendez, E; Barroeta, S et al. (1992) Cutaneous leishmaniasis in western Venezuela caused by infection with Leishmania venezuelensis and L. braziliensis variants. Trans R Soc Trop Med Hyg 86:141-8
McMahon-Pratt, D; Traub-Cseko, Y; Lohman, K L et al. (1992) Loss of the GP46/M-2 surface membrane glycoprotein gene family in the Leishmania braziliensis complex. Mol Biochem Parasitol 50:151-60
Rivas, L; Kahl, L; Manson, K et al. (1991) Biochemical characterization of the protective membrane glycoprotein GP46/M-2 of Leishmania amazonensis. Mol Biochem Parasitol 47:235-43
White Jr, A C; Hanham, C (1991) Species and stage specificity of Leishmania donovani antigens. J Parasitol 77:142-50

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