The goal of this work is to study the structure and function of the immunoglobulin molecule. The work is being performed so that this understanding will be applied to the development of antibodies for human therapy. A. Therapeutic systems. 1. Antibodies to surface antigens of group B streptococci (GBS) have been demonstrated to have protective efficacy in a model of neonatal sepsis. We have identified colony opacity variants of GBS, studied their interactions with host defenses, and shown that opacity differences are even more marked in clinical isolates than in the laboratory strains previously analyzed. 2. The efficacy of anti-HIV antibodies coupled to ricin A-chain has been studied in vitro. Antibodies directed against different envelope epitopes have been tested. Biological variants of HIV that escape killing with these immunotoxins and CD4-PE40 have been identified. The phenotype of the cells carrying these HIV has been studied, and the molecular mechanisms of immunotoxin escape have been evaluated. Immunotoxins are being tested in vivo in well-studied animal systems. 3. Evaluation of the anti-HIV antibody response in subjects exposed to the IIIB/LAV isolate of HIV. Subjects include humans and chimpanzees infected with the virus or immunized with envelope subunits.
