NEUTRALIZATION OF HIV-1 PRIMARY ISOLATES BY POLYCLONAL AND MONOCLONALHUMAN-ANTIBODIES

To examine antibody-mediated neutralization of HIV-1 primary isolates in vitro, we tested sera and plasma from infected individuals against four clade B primary isolates, These isolates were analyzed further fo r neutralization by a panel of several human anti-HIV-l mAb in order t o identify the neutralizing epitopes of these viruses, Each of the HIV -1(+) serum and plasma specimens tested had neutralizing activities ag ainst one or more of the four primary isolates, Of the three individua l sera, one (FDA-2) neutralized all of the four isolates, while the ot her two sera were effective against only one virus, The pooled plasma and serum samples reacted broadly with these isolates, Based on the ne utralizing activities of the mAb panel, each virus isolate exhibited a distinct pattern of reactivity, suggesting antigenic diversity among clade B viruses, Neutralizing epitopes were found in the V3 loop and C D4-binding domain of gp120, as well as near the transmembrane region ( cluster II epitope) of gp41, A mAb directed to the cluster I epitope o f gp41 near the immunodominant disulfide loop weakly neutralized one p rimary isolate, None of the mAb in the panel affected one primary isol ate, US4, although this virus was sensitive to neutralization by some of the polyclonal antibody specimens, This isolate was also resistant to neutralization by a cocktail of 10 mAb, most of which individually inhibited at least one of the other three viruses tested, These result s suggest that neutralizing activity for this latter virus is present in certain HIV-1(+) sera/plasma, but is not exhibited by the mAb in th e panel, Thus, effective neutralizing antibodies against primary isola tes can be generated by humans upon exposure to HIV-1, but not all of these antigenic specificities are represented in a large panel of huma n anti-HIV-1 mAb.