The long-term objective of this project is to develop antibodies and anti-idiotypic antibodies targeting the relatively conserved core structure of gp4l as prophylactic and therapeutic strategies blocking HIV-1 entry. Synthetic peptides N36 and C34, corresponding to the relatively conserved sequences of the N and C-terminal coiled-coil regions of gp4l, have been shown each to inhibit HIV-1 env-mediated membrane fusion and, upon mixing at equimolar concentration, form a stable alpha-helical trimer of heterodimers, representing the fusion-active conformational core structure of gp4l.
The specific aims of this project are: 1) to generate polyclonal antibodies against N36, C34 and the N36/C34 complex, in order to determine whether or not the antibodies recognize the tertiary and quaternary structure of the corresponding relatively conserved regions in gp4l, interact with the fusion-active conformational core domain, and inhibit HIV-1 infection; 2) to induce polyclonal and monoclonal anti-idiotypic antibodies against IgG antibodies to N36, C34 and the N36/C34 complex, in order to determine whether or not the anti-idiotypic antibodies mimic the functions of these peptides and inhibit HIV-1 env-mediated membrane fusion; and 3) to utilize these antibodies and anti-idiotypic antibodies to study the mechanism of peptide-mediated inhibition of membrane fusion initiated by HIV-1.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21AI042693-01
Application #
2555247
Study Section
Special Emphasis Panel (ZAI1-DET-A (O2))
Project Start
1997-09-30
Project End
1999-09-29
Budget Start
1997-09-30
Budget End
1998-09-29
Support Year
1
Fiscal Year
1997
Total Cost
Indirect Cost
Name
New York Blood Center
Department
Type
DUNS #
City
New York
State
NY
Country
United States
Zip Code
10065
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Jiang, S; Lin, K; Lu, M (1998) A conformation-specific monoclonal antibody reacting with fusion-active gp41 from the human immunodeficiency virus type 1 envelope glycoprotein. J Virol 72:10213-7