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

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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 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.

Original languageEnglish
Article number122466
Pages (from-to)182-191
Number of pages10
JournalJournal of Clinical Investigation
Volume129
Issue number1
DOIs
Publication statusPublished - 2 Jan 2019

Cite this

Parsons, M. S., Lee, W. S., Kristensen, A. B., Amarasena, T., Khoury, G., Wheatley, A. K., ... Kent, S. J. (2019). Fc-dependent functions are redundant to efficacy of anti-HIV antibody PGT121 in macaques. Journal of Clinical Investigation, 129(1), 182-191. [122466]. https://doi.org/10.1172/JCI122466