Abstract

This proposal is primarily focused on delineating the antigens relevant for protective immunity against leishmaniasis and clinical diagnosis of the disease (i.e., Kala-azar) as well as developing a further understanding of the biology of the parasite (i.e., its survival within its insect and mammalian hosts). The projects will involve the disciplines of biology, immunology, molecular biology and biochemistry. Monoclonal antibodies and molecular biology techniques will be used to identify and isolate molecules (stage specific and protective) of Leishmania.
The specific aims of the proposal are: 1. Development of a reliable, specific serological diagnostic assay for visceral leishmaniasis. 2. Identification of antigens protective against infection with Leishmania donovani. 3. Further production of amastigote specific monoclonal antibodies to the amastigote stage. 4. Biochemical, biological and molecular biological characterization of stage-specific antigens (promastigote and amastigote) of Leishmania. 5. Evaluation of stage-specific antigens effectiveness of producing protective immunity in in vivo model systems. 6. Elucidation of mechanisms involved in protective immunity produced to both stage specific and cross-reactive antigens. 7. Analysis of Leishmania antigens on infected macrophages.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
1R01AI023004-01
Application #
3134803
Study Section
Tropical Medicine and Parasitology Study Section (TMP)
Project Start
1985-06-01
Project End
1988-05-31
Budget Start
1985-06-01
Budget End
1986-05-31
Support Year
1
Fiscal Year
1985
Total Cost
Indirect Cost

  Institution

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

  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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