Temporal development and prognostic value of antibody response to the major neutralizing epitopes of gp120 during HIV-1 infection.

Our objective was to analyse the humoral response to the major neutralizing 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 seroconverters. V3 Abs were titrated using 2 different indirect EIAs with synthetic oligopeptides coated on the solid phase. The sequences of the 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 titers were determined using an EIA in which serum antibodies compete with a labeled human monoclonal antibody, F105, whose corresponding epitope overlaps the conformation-dependent CD4BS, for binding to purified recombinant gp120 coated on a solid phase. The prognostic value of both 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 sero-converters were positive for V3 Abs and CD4BS Abs, respectively, during the observation period. V3 Abs were detected first 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 of antibodies appeared simultaneously in 4 patients (20%). No prognostic 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 clearance of viremia in primary HIV-1 infection. These antibodies were not associated with progression to symptomatic infection and are thus of no value for surveillance in HIV-1 infected patients.