Journal article

Fc-dependent functions are redundant to efficacy of anti-HIV antibody PGT121 in macaques

Matthew S Parsons, Wen Shi Lee, Anne B Kristensen, Thakshila Amarasena, Georges Khoury, Adam K Wheatley, Arnold Reynaldi, Bruce D Wines, P Mark Hogarth, Miles P Davenport, Stephen J Kent

JOURNAL OF CLINICAL INVESTIGATION | AMER SOC CLINICAL INVESTIGATION INC | Published : 2019

Abstract

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 mediator..

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