Research Project
3488830
One of the most urgent challenge facing the medical community is the development of effective therapeutic agents for victims of the worldwide AIDS epidemic. Because of their high degree of specificity and high specialized effector functions, monoclonal anti-HIV envelope protein antibodies are considered to be promising candidates for meeting this challenge. As the exact amino acid sequence of the envelope protein (gp160) on HIV types can vary greatly, the overall success of such an approach will depend on the identification of virus neutralizing monoclonal antibodies (moAb) that can recognize highly conserved features of the envelope. This proposal describes the rationale, and a procedure for the preparation of a novel antibody chimera that may fulfill these criteria. Though essentially a human delta 1 kappa antibody, the amino acid sequence of one or both pairs of variable regions (V regions) in this chimera will be replaced with the sequence of a single protein domain (E1 domain) of the CD4 molecule. CD4 is the cellular receptor for HIV. The E1 domain of CD4 is probably sufficient to express full virus binding. It shares significant structural homology with immunoglobulin (Ig) V domains. Since all HIV types seem to use CD4 as their cellular receptor, this CD4/Ab chimera (E1/Ab) may provide a convenient route to a group specific therapeutic agent.
