DEVELOPMENT OF THE ANTI-GPL20 ANTIBODY-RESPONSE DURING SEROCONVERSIONTO HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1

We have studied the development of the antibody response to the surfac e glycoprotein gp120 of human immunodeficiency virus type 1 in three i ndividuals who presented with primary human immunodeficiency virus typ e 1 infection syndrome. Serum anti-gp120 antibodies were first detecte d 4 to 23 days after presentation, after p24 antigen and infectious-vi rus titers in the peripheral blood had declined manyfold from their hi ghest values. Whether anti-gp120 antibodies present at undetectable le vels are involved in clearance of viremia remains unresolved. Among th e earliest detectable anti-gp120 antibodies were those to conformation ally sensitive epitopes; these antibodies were able to block the bindi ng of gp120 monomers to soluble CD4 or to a human monoclonal antibody to a discontinuous epitope overlapping the CD4-binding site. Some of t hese antibodies were type specific to a degree, in that they were more effective at blocking ligand binding to autologous gp120 than to hete rologous gp120. However, the appearance of these antibodies did not co rrelate with that of antibodies able to neutralize the autologous viru s in vitro by a peripheral blood mononuclear cell-based assay. Antibod ies to the V3 loop were detected at about the same time as, or slightl y later than, those to the CD4-binding site. There was a weak correlat ion between the presence of antibodies to the V3 loop and autologous v irus-neutralizing activity in two of three individuals studied. Howeve r, serum from the third individual contained V3 antibodies but lacked the ability to neutralize the autologous virus in vitro, even immediat ely after seroconversion. Thus, no simple, universal correlate of auto logous virus-neutralizing activity in a peripheral blood mononuclear c ell-based assay is apparent from in vitro assays that rely on detectin g antibody interactions with monomeric gp120 or fragments thereof.