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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.

Author information

1
Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, and.
2
ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, The University of Melbourne, Parkville, Victoria, Australia.
3
Kirby Institute, University of New South Wales, Sydney, New South Wales, Australia.
4
Centre for Biomedical Research, Burnet Institute, Melbourne, Victoria, Australia.
5
Melbourne Sexual Health Centre and Department of Infectious Diseases, Alfred Health, Central Clinical School, Monash University, Melbourne, Victoria, Australia.

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.

KEYWORDS:

AIDS vaccine; AIDS/HIV; Immunology

PMID:
30475230
DOI:
10.1172/JCI122466
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