Harnessing Antibody-Dependent Cellular Cytotoxicity To Control HIV-1 Infection

Abstract

Passive administration of broadly neutralizing anti-human immunodeficiency virus type 1 (HIV-1) antibodies (bNAbs) has been recently suggested as a promising alternative therapeutic approach for HIV-1 infection. Although the success behind the studies that used this approach has been attributed to the potency and neutralization breadth of anti-HIV-1 antibodies, several lines of evidence support the idea that specific antibody-dependent effector functions, particularly antibody-dependent cellular cytotoxicity (ADCC), play a critical role in controlling HIV-1 infection. In this review, we showed that there is a direct association between the activation of ADCC and better clinical outcomes. This, in turn, suggests that ADCC could be harnessed to control HIV-1 infection. To this end, we addressed the passive administration of bNAbs capable of selectively activating ADCC responses to HIV-1 patients. Finally, we summarized the potential barriers that may impede the optimal activation of ADCC during HIV-1 infection and provided strategic solutions to overcome these barriers.

Keywords: Env conformation; Fc-FcγR; HIV-1 controllers; Hypo-/defucosylated Fc broadly neutralizing anti-HIV-1 antibodies (bNAbs); Natural killer (NK) cells; Passive antibody administration.