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J Clin Invest. 2018 Nov 26. pii: 122466. doi: 10.1172/JCI122466. [Epub ahead of print]

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

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Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, and.
ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, The University of Melbourne, Parkville, Victoria, Australia.
Kirby Institute, University of New South Wales, Sydney, New South Wales, Australia.
Centre for Biomedical Research, Burnet Institute, Melbourne, Victoria, Australia.
Melbourne Sexual Health Centre and Department of Infectious Diseases, Alfred Health, Central Clinical School, Monash University, Melbourne, Victoria, Australia.


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.


AIDS vaccine; AIDS/HIV; Immunology

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