TY - JOUR AU - Parsons, Matthew S. AU - Lee, Wen Shi AU - Kristensen, Anne B. AU - Amarasena, Thakshila AU - Khoury, Georges AU - Wheatley, Adam K. AU - Reynaldi, Arnold AU - Wines, Bruce D. AU - Hogarth, P. Mark AU - Davenport, Miles P. AU - Kent, Stephen J. T1 - Fc-dependent functions are redundant to efficacy of anti-HIV antibody PGT121 in macaques PY - 2019/01/02/ AB - A considerable body of evidence suggests that Fc-dependent functions improve the capacity of broadly neutralizing antibodies (BnAbs) to protect against and control HIV-1 infection. This phenomenon, however, has not been formally tested in robust cell-associated macaque simian-human immunodeficiency virus (SHIV) models with newer-generation BnAbs. We studied both the WT BnAb PGT121 and a LALA mutant of PGT121 (which has impaired Fc-dependent functions) for their ability to protect pigtail macaques from an i.v. high-dose cell-associated SHIVSF162P3 challenge. We found that both WT and LALA PGT121 completely protected all 12 macaques studied. Further, partial depletion of NK cells, key mediators of Fc-dependent functions, did not abrogate the protective efficacy of PGT121 in 6 macaques. Additionally, in animals with established SHIVSF162P3 infection, SHIV viremia levels were equally rapidly reduced by LALA and WT PGT121. Our studies suggest that the potent neutralizing capacity of PGT121 renders the Fc-dependent functions of the Ab at least partially redundant. These findings have implications for Ab-mediated protection from and control of HIV-1 infection. JF - The Journal of Clinical Investigation JA - J Clin Invest SN - 0021-9738 DO - 10.1172/JCI122466 VL - 129 IS - 1 UR - https://doi.org/10.1172/JCI122466 SP - 182 EP - 191 PB - The American Society for Clinical Investigation ER -