Paper

Human neutralizing antibodies against SARS-CoV-2 require intact Fc effector functions and monocytes for optimal therapeutic protection

Chen, Rita E, Sutton, Rachel E, Carnahan, Robert H, Gilchuk, Pavlo, Jang, Hyesun, Ross, Ted M, Head, Richard D, Bailey, Adam L, Allen, James D, Case, James Brett, Crowe, James E, Mack, Matthias, Zost, Seth J, Huang, Ying, Diamond, Michael S, Winkler, Emma S, Darling, Tamarand L, Boon, Adrianus C M, Yu, Jinsheng

2020

Overview

in vivo is incompletely understood. Here, we define correlates of protection of neutralizing human monoclonal antibodies (mAbs) in SARS-CoV-2-infected animals. Whereas Fc effector functions are dispensable when representative neutralizing mAbs are administered as prophylaxis, they are required for optimal protection as therapy. When given after infection, intact mAbs reduce SARS-CoV-2 burden and lung disease in mice and hamsters better than loss-of-function Fc variant mAbs. Fc engagement of neutralizing antibodies mitigates inflammation and improves respiratory mechanics, and transcriptional profiling suggests these phenotypes are associated with diminished innate immune signaling and preserved tissue repair. Immune cell depletions establish that neutralizing mAbs require monocytes for therapeutic efficacy. Thus, potently neutralizing mAbs require Fc effector functions for maximal therapeutic benefit during therapy to modulate protective immune responses and mitigate lung disease. Competing Interest Statement M.S.D. is a consultant for Inbios, Vir Biotechnology, NGM Biopharmaceuticals, Carnival Corporation and on the Scientific Advisory Boards of Moderna and Immunome. The Diamond laboratory has received unrelated funding support in sponsored research agreements from Moderna, Vir Biotechnology, and Emergent BioSolutions. J.E.C. has served as a consultant for Eli Lilly and Luna Biologics, is a member of the Scientific Advisory Boards of CompuVax and Meissa Vaccines and is Founder of IDBiologics. The Crowe laboratory at Vanderbilt University Medical Center has received sponsored research agreements from AstraZeneca and IDBiologics. Vanderbilt University has applied for patents related to antibodies described in this paper. The Boon laboratory has received unrelated funding support in sponsored research agreements from AI Therapeutics, GreenLight Biosciences, AbbVie, and Nano Targeting & Therapy Biopharma. Footnotes * ↵¶ Lead Contact: Michael S. Diamond, M.D., Ph.D.,

• Publisher: Cold Spring Harbor Laboratory Press,Cold Spring Harbor Laboratory
• Subject: Antibodies / Biotechnology / Disease prevention / Immune response / Immunology / Laboratories / Lung diseases / Monoclonal antibodies / Monocytes / Pharmacology / Phenotypes / Severe acute respiratory syndrome coronavirus 2 / Transcription