TEMPORAL DEVELOPMENT AND PROGNOSTIC VALUE OF ANTIBODY-RESPONSE TO THEMAJOR NEUTRALIZING EPITOPES OF GP120 DURING HIV-1 INFECTION

Our objective was to analyse the humoral response to the major neutral izing epitopes of gp120. The kinetics of the appearance of antibodies directed to the V3 region (V3 Abs) and antibodies directed to the CD4 binding site (CD4BS Abs) were compared in sequential sera from 20 sero converters. V3 Abs were titrated using 2 different indirect EIAs with synthetic oligopeptides coated on the solid phase. The sequences of th e oligopeptides used were those of the MN isolate or a mixture of the consensus sequences of the 5 major HIV-1 subtypes (A-E). CD4BS Abs tit ers were determined using an EIA in which serum antibodies compete wit h a labeled human monoclonal antibody, F105, whose corresponding epito pe overlaps the conformation-dependent CD4BS, for binding to purified recombinant gp120 coated on a solid phase. The prognostic value of bot h antibodies was analyzed in a longitudinal study of 60 HIV-1 infected patients (17 nonprogressors and 43 progressors). Eighty-five percent and 70% of HIV seroconverters were positive for V3 Abs and CD4BS Abs; respectively, during the observation period. V3 Abs were detected firs t in the majority of the patients (mean delay of appearance, 1.22 +/- 0.96 months vs. 4.81 +/- 2.05 months for CD4BS Abs). Both categories o f antibodies appeared simultaneously in 4 patients (20%). No prognosti c value could be attributed to these antibodies. Our data confirm that V3 Abs and CD4BS Abs appear with some delay after primary infection, suggesting that they do not play a large or early role in the rapid cl earance of viremia in primary HIV-1 infection. These antibodies were n ot associated with progression to symptomatic infection and are thus o f no value for surveillance in HIV-1 infected patients. (C) 1997 Wiley -Liss, Inc.