Nucleocapsid-specific antibody function is associated with therapeutic benefits from COVID-19 convalescent plasma therapy
Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:3 |
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| Enthalten in: |
Cell reports. Medicine - 3(2022), 11 vom: 15. Nov., Seite 100811 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Herman, Jonathan D [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 21.11.2022 Date Revised 06.11.2023 published: Print-Electronic ClinicalTrials.gov: NCT04397757 Citation Status MEDLINE |
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| doi: |
10.1016/j.xcrm.2022.100811 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM348650531 |
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| 100 | 1 | |a Herman, Jonathan D |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Nucleocapsid-specific antibody function is associated with therapeutic benefits from COVID-19 convalescent plasma therapy |
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| 500 | |a Date Completed 21.11.2022 | ||
| 500 | |a Date Revised 06.11.2023 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a ClinicalTrials.gov: NCT04397757 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved. | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Randomized Controlled Trial | |
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a COVID immunomodulation | |
| 650 | 4 | |a COVID-19 | |
| 650 | 4 | |a Fc effector functions | |
| 650 | 4 | |a SARS-CoV-2 | |
| 650 | 4 | |a antibody Fc glycosylation | |
| 650 | 4 | |a convalescent plasma | |
| 650 | 4 | |a functional antibodies | |
| 650 | 4 | |a immunodominance shift | |
| 650 | 4 | |a nucleocapsid | |
| 650 | 4 | |a systems serology | |
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| 700 | 1 | |a Wang, Chuangqi |e verfasserin |4 aut | |
| 700 | 1 | |a Burke, John Stephen |e verfasserin |4 aut | |
| 700 | 1 | |a Zur, Yonatan |e verfasserin |4 aut | |
| 700 | 1 | |a Compere, Hacheming |e verfasserin |4 aut | |
| 700 | 1 | |a Kang, Jaewon |e verfasserin |4 aut | |
| 700 | 1 | |a Macvicar, Ryan |e verfasserin |4 aut | |
| 700 | 1 | |a Taylor, Sabian |e verfasserin |4 aut | |
| 700 | 1 | |a Shin, Sally |e verfasserin |4 aut | |
| 700 | 1 | |a Frank, Ian |e verfasserin |4 aut | |
| 700 | 1 | |a Siegel, Don |e verfasserin |4 aut | |
| 700 | 1 | |a Tebas, Pablo |e verfasserin |4 aut | |
| 700 | 1 | |a Choi, Grace H |e verfasserin |4 aut | |
| 700 | 1 | |a Shaw, Pamela A |e verfasserin |4 aut | |
| 700 | 1 | |a Yoon, Hyunah |e verfasserin |4 aut | |
| 700 | 1 | |a Pirofski, Liise-Anne |e verfasserin |4 aut | |
| 700 | 1 | |a Julg, Boris D |e verfasserin |4 aut | |
| 700 | 1 | |a Bar, Katharine J |e verfasserin |4 aut | |
| 700 | 1 | |a Lauffenburger, Douglas |e verfasserin |4 aut | |
| 700 | 1 | |a Alter, Galit |e verfasserin |4 aut | |
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