Effector function does not contribute to protection from virus challenge by a highly potent HIV broadly neutralizing antibody in nonhuman primates

Lars Hangartner; David Beauparlant; Eva Rakasz; Rebecca Nedellec; Nathanaël Hozé; Katherine McKenney; Mauricio A Martins; Gemma E Seabright; Joel D Allen; Andrea M Weiler; Thomas C Friedrich; Roland R Regoes; Max Crispin; Dennis R Burton

doi:10.1126/scitranslmed.abe3349

Back

Effector function does not contribute to protection from virus challenge by a highly potent HIV broadly neutralizing antibody in nonhuman primates

Journal article

Peer reviewed

Effector function does not contribute to protection from virus challenge by a highly potent HIV broadly neutralizing antibody in nonhuman primates

Lars Hangartner, David Beauparlant, Eva Rakasz, Rebecca Nedellec, Nathanaël Hozé, Katherine McKenney, Mauricio A Martins, Gemma E Seabright, Joel D Allen, Andrea M Weiler, …

Science translational medicine, Vol.13(585), p.eabe3349

2021-03-17

DOI: https://doi.org/10.1126/scitranslmed.abe3349

PMID: 33731434

Abstract

Protection from immunodeficiency virus challenge in nonhuman primates (NHPs) by a first-generation HIV broadly neutralizing antibody (bnAb) b12 has previously been shown to benefit from interaction between the bnAb and Fcγ receptors (FcγRs) on immune cells. To investigate the mechanism of protection for a more potent second-generation bnAb currently in clinical trials, PGT121, we carried out a series of NHP studies. These studies included treating with PGT121 at a concentration at which only half of the animals were protected to avoid potential masking of FcγR effector function benefits by dominant neutralization and using a new variant that more completely eliminated all rhesus FcγR binding than earlier variants. In contrast to b12, which required FcγR binding for optimal protection, we concluded that PGT121-mediated protection is not augmented by FcγR interaction. Thus, for HIV-passive antibody prophylaxis, these results, together with existing literature, emphasize the importance of neutralization potency for clinical antibodies, with effector function requiring evaluation for individual antibodies.

Metrics

7 Record Views

22 Times Cited - Web of Science

See more details

InCites Highlights

These are selected metrics from InCites Benchmarking & Analytics tool, related to this output

Collaboration types: Domestic collaboration; International collaboration
Citation topics: 1 Clinical & Life Sciences; 1.66 HIV; 1.66.46 HIV-1
Web Of Science research areas: Cell Biology; Medicine, Research & Experimental
ESI research areas: Biology & Biochemistry

UN Sustainable Development Goals (SDGs)

This output has contributed to the advancement of the following goals:

Source: InCites

Details

Title: Effector function does not contribute to protection from virus challenge by a highly potent HIV broadly neutralizing antibody in nonhuman primates
Creators: Lars Hangartner - Department of Immunology and Microbiology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA., Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA 92037, USA
David Beauparlant - Department of Immunology and Microbiology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
Eva Rakasz - Wisconsin National Primate Research Center, University of Wisconsin-Madison, 1220 Capitol Court, Madison, WI 53715, USA
Rebecca Nedellec - Department of Immunology and Microbiology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
Nathanaël Hozé - Institute of Integrative Biology (IBZ), ETH Zurich, ETH Zentrum, CHN H76.2, Universitätstrasse 16, 8092 Zurich, Switzerland., Theoretical Biology, ETH Zurich, ETH Zentrum, CHN K12.2, Universitätstrasse 16, 8092 Zurich, Switzerland
Katherine McKenney - Department of Immunology and Microbiology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
Mauricio A Martins - Department of Immunology and Microbiology, Scripps Research, Jupiter, FL 33458, USA
Gemma E Seabright - School of Biological Sciences, University of Southampton, Southampton SO17 1BJ, UK., Department of Biochemistry, University of Oxford, Oxford OX1 3QU, UK
Joel D Allen - School of Biological Sciences, University of Southampton, Southampton SO17 1BJ, UK
Andrea M Weiler - Wisconsin National Primate Research Center, University of Wisconsin-Madison, 1220 Capitol Court, Madison, WI 53715, USA
Thomas C Friedrich - Wisconsin National Primate Research Center, University of Wisconsin-Madison, 1220 Capitol Court, Madison, WI 53715, USA
Roland R Regoes - Institute of Integrative Biology (IBZ), ETH Zurich, ETH Zentrum, CHN H76.2, Universitätstrasse 16, 8092 Zurich, Switzerland., Theoretical Biology, ETH Zurich, ETH Zentrum, CHN K12.2, Universitätstrasse 16, 8092 Zurich, Switzerland
Max Crispin - School of Biological Sciences, University of Southampton, Southampton SO17 1BJ, UK
Dennis R Burton - Department of Immunology and Microbiology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA., Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA 92037, USA., IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA., Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, Harvard University, Cambridge, MA 02139, USA
Publication Details: Science translational medicine, Vol.13(585), p.eabe3349
Language: English
Resource Type: Journal article
PMID: 33731434
Record Identifier: 991031613543702976