RELEVANCE OF THE ANTIBODY-RESPONSE AGAINST HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 ENVELOPE TO VACCINE DESIGN

Understanding the antibody response in HIV-I infection is important to vaccine design. We have studied the antibody response to HIV-I envelo pe at the molecular level and determined the characteristics of neutra lizing and non-neutralizing antibodies. These antibodies were isolated from phage display libraries prepared from long-term seropositive asy mptomatic individuals. The HIV-1 envelope is presented to the immune s ystem in several antigenically distinct configurations: unprocessed gp 160, gp120 and gp41 subunits and native envelope, each of which may be important in eliciting an antibody response in HIV-1 infection. The a ntibodies tested characteristically had poor affinities for native env elope as expressed on the surface of virions or infected cells, but ha d high affinities against non-native forms of HIV-I envelope (viral de bris). An exceptionally potent neutralizing antibody in contrast, boun d native envelope with equivalent or somewhat higher affinity than thi s. This indicates that the antibody response in HIV-I infection is pri ncipally elicited by viral debris rather than virions, and that these antibodies bind and neutralize viruses sub-optimally. Potential vaccin es should be designed to elicit responses against native envelope. (C) 1997 Elsevier Science B.V.