Broadly Neutralizing Antibodies Elicited by the Hypervariable Neutralizing Determinant of HIV-1

The principal neutralizing determinant (PND) of human immunodeficiency virus (HIV)-1 resides within the V$_3$ loop of the envelope protein. Antibodies elicited by peptides of this region were able to neutralize diverse isolates. Serum from one of three animals immunized with the human T cell lymphoma virus (HTLV)-III$_{MN}$ PND peptide, RP142, neutralized MN and the sequence-divergent HTLV-III$_B$ isolate. Serum from one of three animals immunized with a 13-amino acid III$_B$ PND peptide (RP337) also neutralized both of these isolates. Characterization of these sera revealed that the cross-neutralizing antibodies bound the amino acid sequence GlyPro-GlyArgAlaPhe (GPGRAF) that is present in both isolates. This sequence is frequently found in the PNDs analyzed in randomly selected HIV-1 isolates. Sera from two rabbits immunized with a peptide containing only the GPGRAF residues neutralized divergent isolates, including III$_B$ and MN.