Neonates born from human immunodeficiency virus (HIV)-infected mothers are currently identified as a high risk group in Western and Third World countries. It is the aim of this proposal to engineer antibody molecules that can be used for passive immunotherapy to prevent neonatal HIV infection. This project is based on a) the notion that the interaction between the CD4 receptor/molecule on T lymphocytes and HIV is a central feature in HIV infection, and b) a plausible prediction that interference with this interaction could guarantee protection. Protein engineering techniques will be used to construct antibodies that possess the HIV-binding domain of the CD4 receptor/molecule on immune cells, receptor (CD4)-like antibodies. This goal will be pursued by inserting discrete CD4 peptides from the putative HIV-binding site in the form of synthetic oligonucleotides into the immunoglobulin heavy- or light-chain gene, or both genes. These constructs will be expressed in mammalian cells by electroporation. The obtained CD4-like antibodies will be tested in vitro, immunochemically and biologically, for a) expression of the engineered HIV-binding domain, b) binding to HIV, and c) inhibition of viral infection of susceptible cells. The work proposed may constitute the basis for a new rational strategy to passive immunotherapy in the prevention of neonatal HIV infection and its consequences.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD025787-03
Application #
3326971
Study Section
Special Emphasis Panel (ARR (V1))
Project Start
1990-05-02
Project End
1993-04-30
Budget Start
1992-05-01
Budget End
1993-04-30
Support Year
3
Fiscal Year
1992
Total Cost
Indirect Cost
Name
University of California San Diego
Department
Type
Schools of Medicine
DUNS #
077758407
City
La Jolla
State
CA
Country
United States
Zip Code
92093