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
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..View full abstract
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Awarded by Australian National Health and Medical Research Council (NHMRC)
We acknowledge S. Alcantara, S. Pantham, A. Owen, M. Schepers, and C. McClumpha (all from The University of Melbourne) for expert assistance with animal care and sample processing. This work was funded by grants from the Australian National Health and Medical Research Council (NHMRC) (grants 1101813, 1124680, 1052979, and 1136322) and the Australian Centre for HIV and Hepatitis Virology Research (to SJK and/or MSP).