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

Abstract

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 peptides comprised residues 299-317 (numbering of HIV1 MN) in the N-terminal half of the V3 loop of the envelope glycoprotein gp120 and were derived from the sequences of autologous, as well as heterologous isolates. All four individuals studied lacked anti-V3 IgG binding to at least one autologous V3 sequence. V3 peptides to which autologous sera 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 per se and that the respective human hosts have selective defects in recognising the corresponding V3 sequences. Despite the absence of antibody binding to autologous V3 peptides, the human sera had neutralising antibodies to autologous (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 variants with amino acid substitutions close to the crown of the V3 loop or in regions outside the sequence corresponding to peptides used for immunisation. The amino acid exchanges affected V3 positions known to be antigenic and which are also prone to change successively in infected persons. It is likely that neutralising antibodies recognise both linear and conformational epitopes in the V3 loop. Apparently, there are several, but restricted, numbers of ways for this structure to change its conformation and thereby give rise to neutralisation resistant viruses.

Production of a Short Recombinant C4V3 HIV-1 Immunogen That Induces Strong Anti-HIV Responses by Systemic and Mucosal Routes Without the Need of Adjuvants

“…The B cell epitope comprises the core of the V3 loop, a sequence known for being effective at eliciting neutralizing antibodies (31), and even partial protection in monkeys against SHIV challenges (22). In addition, this epitope overlaps a CTL region that is effective in controlling viral replication (3,32).…”

Dissecting the Neutralizing Antibody Specificities of Broadly Neutralizing Sera from Human Immunodeficiency Virus Type 1-Infected Donors

“…Most studies mapping serum NAb specificities have focused generally on immunized animals, whose sera typically exhibit weak neutralization of primary isolates (5,31,36,46,71). Similarly, sera from naturally infected individuals and vaccine recipients that have been mapped tend to show weak to moderate neutralization (4,44,47,52,77). These studies have largely approached the problem of mapping polyclonal sera specificities by examining binding titers to a range of HIV-1 antigens and peptides or through the use of neutralization competition assays.…”

A Peptide & Peptide Nucleic Acid Synthesis Technology for Transporter Molecules and Theranostics - The SPPS

“…The antibody reactivity of 34 Swedish, 30 Tanzanian and 42 Zimbabwean HIV-1-positive sera to 67 synthetic peptides, synthesized by SPPS, were investigated and compared with sequences from North American and African HIV-1 isolates, derived from regions of gag and env known to be antigenic 49, 51, 52.…”