Neutralization of HIV-1 primary isolates by polyclonal and monoclonal human antibodies

To examine antibody-mediated neutralization of HIV-1 primary isolates invitro, we tested sera and plasma from infected individuals against fourclade B primary isolates. These isolates were analyzed further forneutralization by a panel of several human anti-HIV-1 mAb in order toidentify the neutralizing epitopes of these viruses. Each of the HIV-1+serum and plasma specimens tested had neutralizing activities against oneor more of the four primary isolates. Of the three individual sera, one(FDA-2) neutralized all of the four isolates, while the other two sera wereeffective against only one virus. The pooled plasma and serum samplesreacted broadly with these isolates. Based on the neutralizing activitiesof the mAb panel, each virus isolate exhibited a distinct pattern ofreactivity, suggesting antigenic diversity among clade B viruses.Neutralizing epitopes were found in the V3 loop and CD4- binding domain ofgp120, as well as near the transmembrane region (cluster II epitope) ofgp41. A mAb directed to the cluster I epitope of gp41 near theimmunodominant disulfide loop weakly neutralized one primary isolate. Noneof the mAb in the panel affected one primary isolate, US4, although thisvirus was sensitive to neutralization by some of the polyclonal antibodyspecimens. This isolate was also resistant to neutralization by a cocktailof 10 mAb, most of which individually inhibited at least one of the otherthree viruses tested. These results suggest that neutralizing activity forthis latter virus is present in certain HIV-1+ sera/plasma, but is notexhibited by the mAb in the panel. Thus, effective neutralizing antibodiesagainst primary isolates can be generated by humans upon exposure to HIV-1,but not all of these antigenic specificities are represented in a largepanel of human anti-HIV-1 mAb.