The geometric increase in the number of individuals infected by human immunodeficiency virus type 1 (HIV-1) has created serious social, economical and life-threatening issues to the human race. It is of pressing concerns to develop effective measures for controlling the spread of this disease. We now propose to develop a specific immunotoxin by chemically coupling a toxin to a group- specific neutralization monoclonal antibody. In addition to its retained ability to neutralize free virions, this immunotoxin can kill HIV-1 infected cell specifically at low concentrations. This cytotoxic property will mediate the elimination of latently infected cells in infected individuals. The long-term objective of the project is to develop a panel of specific and effective immunotoxins as therapeutic agents for AIDS.
The specific aims of this Phase 1 project are: 1. To construct immunotoxins by coupling pokeweed antiviral protein to group specific neutralizing monoclonal antibodies. 2. To determine the ability to which these immunotoxins prevent viral infection and replication after binding to free virions and block syncytium formation between infected cells and CD4 positive cells. 3. To examine the ability of the immunotoxin to kill HIV-l infected cells expressing gp120 on the cell surface.
