@article{09aea8a121f741fa8360e1a3cbccbce2,
title = "Nucleocapsid-specific antibody function is associated with therapeutic benefits from COVID-19 convalescent plasma therapy",
abstract = "Coronavirus disease 2019 (COVID-19) convalescent plasma (CCP), a passive polyclonal antibody therapeutic agent, has had mixed clinical results. Although antibody neutralization is the predominant approach to benchmarking CCP efficacy, CCP may also influence the evolution of the endogenous antibody response. Using systems serology to comprehensively profile severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) functional antibodies of hospitalized people with COVID-19 enrolled in a randomized controlled trial of CCP (ClinicalTrials.gov: NCT04397757), we find that the clinical benefits of CCP are associated with a shift toward reduced inflammatory Spike (S) responses and enhanced nucleocapsid (N) humoral responses. We find that CCP has the greatest clinical benefit in participants with low pre-existing anti-SARS-CoV-2 antibody function and that CCP-induced immunomodulatory Fc glycan profiles and N immunodominant profiles persist for at least 2 months. We highlight a potential mechanism of action of CCP associated with durable immunomodulation, outline optimal patient characteristics for CCP treatment, and provide guidance for development of a different class of COVID-19 hyperinflammation-targeting antibody therapeutic agents.",
keywords = "antibody Fc glycosylation, convalescent plasma, COVID immunomodulation, COVID-19, Fc effector functions, functional antibodies, immunodominance shift, nucleocapsid, SARS-CoV-2, systems serology",
author = "Herman, {Jonathan D.} and Chuangqi Wang and Burke, {John Stephen} and Yonatan Zur and Hacheming Compere and Jaewon Kang and Ryan Macvicar and Sabian Taylor and Sally Shin and Ian Frank and Don Siegel and Pablo Tebas and Choi, {Grace H.} and Shaw, {Pamela A.} and Yoon, {Hyun Ah} and Pirofski, {Liise anne} and Julg, {Boris D.} and Bar, {Katharine J.} and Douglas Lauffenburger and Galit Alter",
note = "Funding Information: We thank Nancy Zimmerman, Mark and Lisa Schwartz, an anonymous donor (financial support), Terry and Susan Ragon, and the SAMANA Kay MGH Research Scholars award for support. We acknowledge support from the Ragon Institute of MGH, MIT and Harvard ; the Massachusetts Consortium on Pathogen Readiness (MassCPR); the NIH ( 3R37AI080289-11S1 , R01AI146785 , U19AI42790-01 , U19AI135995-02 , U19AI42790-01 , 1U01CA260476-01 , CIVIC75N93019C00052 , T32 AI007061 , and 3UL1TR002556 ); the Gates Foundation and the Global Health Vaccine Accelerator Platform ( OPP1146996 and INV-001650 ); and the Musk Foundation . Funding Information: We thank Nancy Zimmerman, Mark and Lisa Schwartz, an anonymous donor (financial support), Terry and Susan Ragon, and the SAMANA Kay MGH Research Scholars award for support. We acknowledge support from the Ragon Institute of MGH, MIT and Harvard; the Massachusetts Consortium on Pathogen Readiness (MassCPR); the NIH (3R37AI080289-11S1, R01AI146785, U19AI42790-01, U19AI135995-02, U19AI42790-01, 1U01CA260476-01, CIVIC75N93019C00052, T32 AI007061, and 3UL1TR002556); the Gates Foundation and the Global Health Vaccine Accelerator Platform (OPP1146996 and INV-001650); and the Musk Foundation. J.D.H. H.Y. L.-a.P. B.D.J. D.L. K.J.B. and G.A. conceived the idea. K.J.B. P.A.S. G.H.C. P.T. D.S. and I.F. designed, conducted, and analyzed the results of the randomized clinical trial. J.D.H. and G.A. designed the experiments. J.D.H. J.S.B. Y.Z. H.C. J.K. R.M. and S.S. performed the antibody profiling experiments. J.D.H. C.W. D.L. and G.A. analyzed the data. J.D.H. C.W. K.J.B. D.L. and G.A. wrote the paper with input from all authors. G.A. is a founder of SeromYx Systems, Inc. an equity holder in Leyden Labs, and a member of the scientific advisory board of Sanofi Pasteur. We support inclusive, diverse, and equitable conduct of research. Publisher Copyright: {\textcopyright} 2022 The Authors",
year = "2022",
month = nov,
day = "15",
doi = "10.1016/j.xcrm.2022.100811",
language = "English (US)",
volume = "3",
journal = "Cell Reports Medicine",
issn = "2666-3791",
publisher = "Cell Press",
number = "11",
}