eCD4-Ig promotes ADCC activity of sera from HIV-1-infected patients

Antibody-dependent cell-mediated cytotoxity (adcc) can eliminate hiv-1 infected cells,and may help reduce the reservoir of latent virus in infected patients. sera of hiv-1 positive individuals include a number of antibodies that recognize epitopes usually occluded on hiv-1 envelope glycoprotein (env) trimers. we have recently described ecd4-ig,a potent and exceptionally broad inhibitor of hiv-1 entry that can be used to protect rhesus macaques from multiple high-dose challenges with simian-human immunodeficiency virus ad8 (shiv-ad8). here we show that ecd4-ig bearing an igg1 fc domain (ecd4-igg1) can mediate efficient adcc activity against hiv-1 isolates with differing tropisms,and that it does so at least 10-fold more efficiently than cd4-ig,even when more cd4-ig molecules bound cell surface-expressed env. an adcc-inactive igg2 form of ecd4-ig (ecd4-igg2) exposes v3-loop and cd4-induced epitopes on cell-expressed trimers,and renders hiv-1-infected cells susceptible to adcc mediated by antibodies of these classes. moreover,ecd4-igg2,but not igg2 forms of the broadly neutralizing antibodies vrc01 and 10–1074,enhances the adcc activities of serum antibodies from patients by 100-fold,and significantly enhanced killing of two latently infected t-cell lines reactivated by vorinostat or tnfα. thus ecd4-ig is qualitatively different from cd4-ig or neutralizing antibodies in its ability to mediate adcc,and it may be uniquely useful in treating hiv-1 infection or reducing the reservoir of latently infected cells. © 2017 davis-gardner et al.