Functional activities of 20 human immunodeficiency virus type 1 (HIV-1)- specific human monoclonal antibodies

Antibodies that are useful in the treatment of HIV infection should result in virus neutralization or lysis of infected cells but should not enhance infection. In this study, the potential clinical use of 20 HIV-1-specific human monoclonal antibodies (HuMAbs) was determined by measuring their neutralizing, antibody-dependent cellular cytotoxicity (ADCC), and complement-mediated antibody-dependent enhancing (C-ADE) activities using HIV(LAI) as the target virus. Two HuMAbs mediated both C-ADE and ADCC, two exclusively neutralized, and five exclusively mediated ADCC. Ten HuMAbs demonstrated no activity in any of the three assays. Three antibodies that neutralized HIV(LAI) were tested against HIV(SF2); all three also neutralized HIV(SF2). Four of five HuMAbs mediating ADCC against HIV(LAI) that were also tested against HIVsv2 had ADCC activity against HIV(SF2). These results demonstrate that many HuMAbs have unique functions, allowing the separation of potentially beneficial and harmful activities. Combinations of HuMAbs with ADCC and neutralizing functions may have therapeutic utility.