V3-specific polyclonal antibodies affinity purified from sera of infected humans effectively neutralize primary isolates of human immunodeficiency virus type 1

Although many human sera possess potent neutralizing activities for primary HIV-1 viruses, such activities are not efficiently induced by the current generation of vaccine candidates, and the epitopes, mediating this neutralization are not known. The V3 loop of gp120 is believed to be the principal neutralization domain of laboratory-adapted viruses, but the importance of this region in neutralization of primary isolates is unclear. This question was explored using polyclonal anti-V3 antibodies purified by immunoaffinity methods from sera of HIV-1-infected patients. To include antibodies that might be directed against conformational and/or glycan-dependent epitopes not presented by synthetic peptides, the antibody isolations were performed with a fusion glycoprotein expressing the native V3 region of JR-CSF, a primary R5 isolate. V3-reactive antibody fractions from all eight sera examined showed potent neutralization of at least one of the three primary HIV-1 isolates tested; four of these antibody preparations neutralized all three primary viruses. For a number of serum-virus combinations 90% neutralization doses (ND(90)) between 1 and 5 mug/ml were obtained, and the most potent anti-V3 fraction had ND(50) values at or below 0.3 mug/ml for all three primary isolates. These neutralization activities against primary viruses were higher than those of potent monoclonal antibodies assayed in the same experiment. These data indicate that the V3 region can be an important neutralization target in primary isolates, and suggest that effective presentation of V3 epitopes in a vaccine formulation might induce protective Immoral responses against natural infection by HIV-1.