POTENT NEUTRALIZATION OF PRIMARY HIV-1 ISOLATES BY ANTIBODIES DIRECTED AGAINST EPITOPES PRESENT IN THE V1 V2 DOMAIN OF HIV-1 GP120/

Although it is known that some human immune sera possess potent neutra lizing activities for primary viruses, the identity of the target epit opes mediating this neutralization is unknown, and currently available immunogens have not been able to induce such activities. Using recomb inant fusion glycoproteins expressing native V1/V2 domains of gp120 we have found that sera from a subset of HIV-1-infected humans contain a ntibodies that recognize broadly conserved V1/V2 epitopes. Such antibo dies were isolated from one human serum by affinity chromatography on a column containing a V1/V2 fusion protein, and shown to efficiently n eutralize several macrophage-tropic HIV-1 isolates. Rodents immunized with the purified V1/V2 fusion protein produced antibodies reactive wi th unrelated V1/V2 fusion proteins and with heterologous gp120s. V1/V2 -specific immunoglobulins isolated from sera of these animals by affin ity chromatography also possessed potent neutralization activity for s everal primary conserved epitopes that mediate potent neutralization o f primary viruses, and suggest that subunit vaccines that efficiently induce such antibodies may provide protective humoral immunity against clinically relevant HIV-1 isolates. (C) 1998 Elsevier Science Ltd. Al l rights reserved.