The purpose of this proposal is to investigate biochemical and immunochemical differences between the life cycle/developmental stages (promastigote - amastigote) of the parasite, Leishmania as these may provide important targets for both chemotherapeutic or vaccine approaches for the control of this disease. This proposal will focus primarily on the antigens/molecules specifically associated with the amastigote stage of Leishmania, to investigate their potential in induction of protective immunity and biological function. Specifically the aims of this proposal are: 1. Biochemical and biological characterization of stage-specific antigens (promastigote and amastigote) of Leishmania. The focus of these studies will be membrane components of the amastigote and flagellar components of the promastigote. 2. Development of methods/strains for the axenic (extracellular) culture of Leishmania amastigotes. 3. Identification and evaluation ( in vivo) of amastigote antigens protective against an infection with Leishmania sp.. 4. Molecular biological studies of stage-specific and protective antigens. Specifically, genes encoding for specific amastigote membrane proteins of L. pifanoi and L. amazonensis and Leishmania flagellar proteins will be studied. If time permits, other genes may be studied.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI027811-02
Application #
3142075
Study Section
Bacteriology and Mycology Subcommittee 2 (BM)
Project Start
1989-04-01
Project End
1992-03-31
Budget Start
1990-04-01
Budget End
1991-03-31
Support Year
2
Fiscal Year
1990
Total Cost
Indirect Cost
Name
Yale University
Department
Type
Schools of Medicine
DUNS #
082359691
City
New Haven
State
CT
Country
United States
Zip Code
06520
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Deak, Eszter; Jayakumar, Asha; Cho, Ka Wing et al. (2010) Murine visceral leishmaniasis: IgM and polyclonal B-cell activation lead to disease exacerbation. Eur J Immunol 40:1355-68
Matza, Didi; Badou, Abdallah; Kobayashi, Koichi S et al. (2008) A scaffold protein, AHNAK1, is required for calcium signaling during T cell activation. Immunity 28:64-74
Carrillo, E; Ahmed, S; Goldsmith-Pestana, K et al. (2007) Immunogenicity of the P-8 amastigote antigen in the experimental model of canine visceral leishmaniasis. Vaccine 25:1534-43