@article{7924c691fd0a46518c508b37bd65b0e8,
title = "Human neutralizing antibodies against SARS-CoV-2 require intact Fc effector functions for optimal therapeutic protection",
abstract = "Neutralizing human monoclonal antibodies (mAbs) against SARS-CoV-2 require Fc effector functions for optimal protection during post-exposure therapy, with intact mAbs reducing SARS-CoV-2 burden and lung disease in rodent models better than LALA-PG loss-of-function Fc variant mAbs and requiring monocytes and CD8+ T cells for optimal clinical and virological benefit.",
keywords = "CD8+ T cells, RNA sequencing, SARS-CoV-2, antibody, effector function, lung, monocytes, mouse model, pathogenesis, therapy",
author = "Winkler, {Emma S.} and Pavlo Gilchuk and Jinsheng Yu and Bailey, {Adam L.} and Chen, {Rita E.} and Zhenlu Chong and Zost, {Seth J.} and Hyesun Jang and Ying Huang and Allen, {James D.} and Case, {James Brett} and Sutton, {Rachel E.} and Carnahan, {Robert H.} and Darling, {Tamarand L.} and Boon, {Adrianus C.M.} and Matthias Mack and Head, {Richard D.} and Ross, {Ted M.} and Crowe, {James E.} and Diamond, {Michael S.}",
note = "Funding Information: M.S.D. is a consultant for Inbios, Vir Biotechnology, NGM Biopharmaceuticals, and Carnival Corporation, and on the Scientific Advisory Boards of Moderna and Immunome. The Diamond laboratory has received 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 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 funding support in sponsored research agreements from AI Therapeutics, GreenLight Biosciences, AbbVie, and Nano Targeting & Therapy Biopharma. R.H. may receive royalty income based on the CompBio technology developed by R.H. and licensed by Washington University to PercayAI. Funding Information: We thank the Pulmonary Morphology Core at Washington University School of Medicine for tissue sectioning. We also thank Joseph Reidy and Andrew Trivette at Vanderbilt Vaccine Center for human antibody sequence analysis and verification, and Rachel Nargi for assistance with mAb purification. This study was supported by the NIH (75N93019C00062, 75N93019C00074, R01 AI157155, and U01 AI15181), the Defense Advanced Research Projects Agency (HR001117S0019), Fast Grants (Mercatus Center, George Mason University), the Dolly Parton COVID-19 Research Fund, and the Future Insight Prize (Merck KGaA to J.E.C.). E.S.W. is supported by NIH (F30 AI152327). J.B.C. is supported by a Helen Hay Whitney Foundation postdoctoral fellowship. This work was also funded by the University of Georgia and Washington University. T.M.R. is supported by the Georgia Research Alliance as an Eminent Scholar. P.G. S.J.Z. R.E.S. and R.H.C. designed and generated human antibodies. E.S.W. A.L.B. and R.E.C. performed mouse experiments. E.S.W. and Z.C. analyzed viral burden and performed immune cell processing. E.S.W. and A.L.B. performed pulmonary mechanics analysis. E.S.W. and J.B.C. performed neutralization analyses. J.Y. and R.H. performed RNA sequencing and analysis. H.J. Y.H. J.D.A. and T.M.R. performed hamster experiments. T.L.D. and A.C.M.B. validated reagents for hamster gene expression. M.M. provided anti-CCR2 antibody. J.E.C. T.M.R. A.C.M.B. and M.S.D. obtained funding and supervised research. E.S.W. and M.S.D. wrote the initial draft, with the other authors providing editorial comments. M.S.D. is a consultant for Inbios, Vir Biotechnology, NGM Biopharmaceuticals, and Carnival Corporation, and on the Scientific Advisory Boards of Moderna and Immunome. The Diamond laboratory has received 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 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 funding support in sponsored research agreements from AI Therapeutics, GreenLight Biosciences, AbbVie, and Nano Targeting & Therapy Biopharma. R.H. may receive royalty income based on the CompBio technology developed by R.H. and licensed by Washington University to PercayAI. Funding Information: We thank the Pulmonary Morphology Core at Washington University School of Medicine for tissue sectioning. We also thank Joseph Reidy and Andrew Trivette at Vanderbilt Vaccine Center for human antibody sequence analysis and verification, and Rachel Nargi for assistance with mAb purification. This study was supported by the NIH ( 75N93019C00062 , 75N93019C00074 , R01 AI157155 , and U01 AI15181 ), the Defense Advanced Research Projects Agency ( HR001117S0019 ), Fast Grants ( Mercatus Center, George Mason University ), the Dolly Parton COVID-19 Research Fund , and the Future Insight Prize ( Merck KGaA to J.E.C.). E.S.W. is supported by NIH ( F30 AI152327 ). J.B.C. is supported by a Helen Hay Whitney Foundation postdoctoral fellowship. This work was also funded by the University of Georgia and Washington University . T.M.R. is supported by the Georgia Research Alliance as an Eminent Scholar. Publisher Copyright: {\textcopyright} 2021 Elsevier Inc.",
year = "2021",
month = apr,
day = "1",
doi = "10.1016/j.cell.2021.02.026",
language = "English",
volume = "184",
pages = "1804--1820.e16",
journal = "Cell",
issn = "0092-8674",
number = "7",
}