NEUTRALIZING ANTIBODIES FROM THE SERA OF HUMAN-IMMUNODEFICIENCY-VIRUSTYPE 1-INFECTED INDIVIDUALS BIND TO MONOMERIC GP120 AND OLIGOMERIC GP140

Antibodies that neutralize primary isolates of human immunodeficiency virus type 1 (HIV-1) appear during HIV-1 infection but are difficult t o elicit by immunization with current vaccine products comprised of mo nomeric forms of HIV-1 envelope glycoprotein gp120. The limited neutra lizing antibody response generated by gp120 vaccine products could be due to the absence or inaccessibility of the relevant epitopes. To det ermine whether neutralizing antibodies from HIV-1-infected patients bi nd to epitopes accessible on monomeric gp120 and/or oligomeric gp140 ( ogp140), purified total immunoglobulin from the sera of two HIV-1-infe cted patients as well as pooled HIV immune globulin were selectively d epleted of antibodies which bound to immobilized gp120 or ogpl40. Afte r passage of each immunoglobulin preparation through the respective co lumns, antibody titers against gp120 and ogp140 were specifically redu ced at least 128-fold. The gp120- and gp140-depleted antibody fraction from each serum displayed reduced neutralization activity against thr ee primary and two T-cell line-adapted (TCLA) HIV-1 isolates. Signific ant residual neutralizing activity, however, persisted in the depleted sera, indicating additional neutralizing antibody specificities, gp12 0- and ogp140-specific antibodies eluted from each column neutralized both primary and TCLA viruses. These data demonstrate the presence and accessibility of epitopes on both monomeric gp120 and ogpl40 that are specific for antibodies that are capable of neutralizing primary isol ates of HIV-1. Thus, the difficulties associated with eliciting neutra lizing antibodies by using current monomeric gp120 subunit vaccines ma y be related less to improper protein structure and more to ineffectiv e immunogen formulation and/or presentation.