Identification of gp120 regions targeted by a highly potent neutralizing antiserum elicited in a chimpanzee inoculated with a primary human immunodeficiency virus type 1 isolate

We have previously reported that a chimpanzee infected with a primary human immunodeficiency virus type 1 (HIV-1) isolate (HIV-1(DH12)) developed an e xtremely potent virus-neutralizing antibody. Immunoglobulin G purified from this animal conferred sterilizing immunity following passive transfer to m acaques which were subsequently challenged with simian immunodeficiency vir us/HIV-1 chimeric virus strain DH12. In addition to being highly strain spe cific, the chimpanzee antiserum did not bind to the V3 loop peptide of HIV- 1(DH12), nor did it block the interaction of gp120 with the CD4 receptor. W hen neutralization was examined in the context of virus particles carrying chimeric envelope glycoproteins, the presence of all five hypervariable reg ions (V1 to V5) was required for optimal neutralization. Virions bearing ch imeric gp120 containing the V1-V2 and V4 regions of HIV-1(DH12) could also be neutralized, but larger quantities of the chimpanzee antiserum were need ed to block infection. These results indicate that the HIV-1 gp120 epitope( s) targeted by the chimpanzee antiserum is highly conformational, involving surface elements contributed by all of the hypervariable domains of the en velope glycoprotein.