IN-VITRO ANTIGEN CHALLENGE OF HUMAN-ANTIBODY LIBRARIES FOR VACCINE EVALUATION - THE HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 ENVELOPE

Human antibody responses, or versions thereof, can be cloned as phage display libraries, In vaccine evaluation, the possibility therefore ex ists of challenging the human response in vitro, rather than in vivo, in order to assist in establishing the most promising vaccine leads, T he characteristics of the antibodies retrieved directly indicate the s trengths and weaknesses of the vaccine at the molecular level, We appl ied this approach to compare recombinant and native human immunodefici ency virus type 1 envelope preparations. We conclude that recombinant gp160, gp140, and, to a lesser extent, gp120 present epitopes around t he CD4 binding site in a conformation different from that of the nativ e multimer and contrary to expected vaccine requirements. Antibodies t o the potently neutralizing b12 epitope mere selected preferentially f rom an immune library by purified human immunodeficiency virus type 1 virions, This suggests that b12 is a major epitope on the virions, in contrast to recombinant envelope preparations, in which related, weakl y neutralizing epitopes predominate. Although the majority of virions in the preparation used are expected to be noninfective, it appears th at they predominantly express a native envelope configuration and woul d be able to elicit potent neutralizing antibodies.