Comparative studies on neutralisation of primary HIV-1 isolates by human sera and rabbit anti-V3 peptide sera

IgG binding to V3 peptides and serum neutralising responses were studied in four HIV-1 infected individuals with progressive disease over a period of 31-70 months. The 18-20 mer pep tides comprised residues 299-317 (numbering of HIV1 MN) in the N-terminal half of the V3 loop of the envelope glycopro tein gp120 and were derived from the sequences of autologous, as well as he terologous isolates. All four individuals studied lacked anti-V3 IgG bindin g to at least one autologous V3 sequence. V3 peptides to which autologous s era lacked binding IgG were all immunogenic in rabbits and induced antisera that were broadly cross-reactive by EIA and broadly cross-neutralising to primary HIV-1 isolates. This indicates that the peptides are immunogenic pe r se and that the respective human hosts have selective defects in recognis ing the corresponding V3 sequences. Despite the absence of antibody binding to autologous V3 peptides, the human sera had neutralising antibodies to a utologous (three out of four cases), as well as heterologous isolates (all cases). Moreover, in vitro exposure of the patients' isolates to autologous neutralising serum or the homologous rabbit antiserum selected for variant s with amino acid substitutions close to the crown of the V3 loop or in reg ions outside the sequence corresponding to peptides used for immunisation. The amino acid exchanges affected V3 positions known to be antigenic and wh ich are also prone to change successively in infected persons. It is likely that neutralising antibodies recognise both linear and conformational epit opes in the V3 loop. Apparently, there are several, but restricted, numbers of ways for this structure to change its conformation and thereby give ris e to neutralisation resistant viruses. (C) 1999 Wiley-Liss, Inc.