The Fc-effector function of COVID-19 convalescent plasma contributes to SARS-CoV-2 treatment efficacy in mice
Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved..
COVID-19 convalescent plasmas (CCPs) are chosen for plasma therapy based on neutralizing titers and anti-Spike immunoglobulin levels. However, CCP characteristics that promote SARS-CoV-2 control are complex and incompletely defined. Using an in vivo imaging approach, we demonstrate that CCPs with low neutralizing (ID50 ≤ 1:250), but moderate to high Fc-effector activity, in contrast to those with poor Fc function, delay mortality and/or improve survival of SARS-CoV-2-challenged K18-hACE2 mice. The impact of innate immune cells on CCP efficacy depended on their residual neutralizing activity. Fractionation of a selected CCP revealed that IgG and Ig(M + A) were required during therapy, but the IgG fraction alone sufficed during prophylaxis. Finally, despite reduced neutralization, ancestral SARS-CoV-2-elicited CCPs significantly delayed Delta and Beta-induced mortality suggesting that Fc-effector functions contribute to immunity against VOCs. Thus, Fc activity of CCPs provide a second line of defense when neutralization is compromised and can serve as an important criterion for CCP selection.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:4 |
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| Enthalten in: |
Cell reports. Medicine - 4(2023), 1 vom: 17. Jan., Seite 100893 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Ullah, Irfan [VerfasserIn] |
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| Links: |
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| Themen: |
ADCC |
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| Anmerkungen: |
Date Completed 20.01.2023 Date Revised 25.09.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.xcrm.2022.100893 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM35096016X |
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| 245 | 1 | 4 | |a The Fc-effector function of COVID-19 convalescent plasma contributes to SARS-CoV-2 treatment efficacy in mice |
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| 520 | |a Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved. | ||
| 520 | |a COVID-19 convalescent plasmas (CCPs) are chosen for plasma therapy based on neutralizing titers and anti-Spike immunoglobulin levels. However, CCP characteristics that promote SARS-CoV-2 control are complex and incompletely defined. Using an in vivo imaging approach, we demonstrate that CCPs with low neutralizing (ID50 ≤ 1:250), but moderate to high Fc-effector activity, in contrast to those with poor Fc function, delay mortality and/or improve survival of SARS-CoV-2-challenged K18-hACE2 mice. The impact of innate immune cells on CCP efficacy depended on their residual neutralizing activity. Fractionation of a selected CCP revealed that IgG and Ig(M + A) were required during therapy, but the IgG fraction alone sufficed during prophylaxis. Finally, despite reduced neutralization, ancestral SARS-CoV-2-elicited CCPs significantly delayed Delta and Beta-induced mortality suggesting that Fc-effector functions contribute to immunity against VOCs. Thus, Fc activity of CCPs provide a second line of defense when neutralization is compromised and can serve as an important criterion for CCP selection | ||
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| 700 | 1 | |a Beaudoin-Bussières, Guillaume |e verfasserin |4 aut | |
| 700 | 1 | |a Symmes, Kelly |e verfasserin |4 aut | |
| 700 | 1 | |a Cloutier, Marc |e verfasserin |4 aut | |
| 700 | 1 | |a Ducas, Eric |e verfasserin |4 aut | |
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| 700 | 1 | |a Laumaea, Annemarie |e verfasserin |4 aut | |
| 700 | 1 | |a Grunst, Michael W |e verfasserin |4 aut | |
| 700 | 1 | |a Dionne, Katrina |e verfasserin |4 aut | |
| 700 | 1 | |a Richard, Jonathan |e verfasserin |4 aut | |
| 700 | 1 | |a Bégin, Philippe |e verfasserin |4 aut | |
| 700 | 1 | |a Mothes, Walther |e verfasserin |4 aut | |
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| 700 | 1 | |a Bazin, Renée |e verfasserin |4 aut | |
| 700 | 1 | |a Finzi, Andrés |e verfasserin |4 aut | |
| 700 | 1 | |a Uchil, Pradeep D |e verfasserin |4 aut | |
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