The Fc-effector function of COVID-19 convalescent plasma contributes to SARS-CoV-2 treatment efficacy in mice
The Fc-effector function of COVID-19 convalescent plasma contributes to SARS-CoV-2 treatment efficacy in mice
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- creativework.keywords - en
- Fc-effector
- convalescent plasma
- ADCC
- COVID-19
- neutrophils
- macrophages
- SARS-CoV-2
- IgG
- IgM
- IgA
- dc.contributor.author
- Ullah, Irfan
- Beaudoin-Bussières, Guillaume
- Symmes, Kelly
- Cloutier, Marc
- Ducas, Eric
- Tauzin, Alexandra
- Laumaea, Annemarie
- Grunst, Michael W.
- Dionne, Katrina
- Richard, Jonathan
- Bégin, Philippe
- Mothes, Walther
- Kumar, Priti
- Bazin, Renée
- Finzi, Andrés
- Uchil, Pradeep D.
- dc.date.accepted
- 2022-12-14
- dc.date.accessioned
- 2024-01-12T14:44:54Z
- dc.date.available
- 2024-01-12T14:44:54Z
- dc.date.issued
- 2022-12-29
- dc.date.submitted
- 2022-06-15
- dc.description.abstract - en
- HIGHLIGHTS •COVID-19 convalescent plasma (CCP) therapy with robust Fc function can protect mice •Fc activity of CCPs can serve as secondary defense when neutralization is compromised •Fc functions facilitate cross-reactive immunity against SARS-CoV-2 variants of concern •Fc functions can serve as one of the key profiles when selecting CCPs for therapy SUMMARY 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.
- dc.identifier.citation
- Ullah I, Beaudoin-Bussières G, Symmes K, et al. The Fc-effector function of COVID-19 convalescent plasma contributes to SARS-CoV-2 treatment efficacy in mice. Cell Reports Medicine. 2023;4(1). doi:https://doi.org/10.1016/j.xcrm.2022.100893
- dc.identifier.doi
- https://doi.org/10.1016/j.xcrm.2022.100893
- dc.identifier.uri
- https://open-science.canada.ca/handle/123456789/1747
- dc.language.iso
- en
- dc.publisher
- Cell Press
- dc.relation.isversionof
- https://open-science.canada.ca/handle/123456789/1744
- dc.rights - en
- Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)
- dc.rights - fr
- Creative Commons Attribution - Pas d'utilisation commerciale - Pas de modification 4.0 International (CC BY-NC-ND 4.0)
- dc.rights.openaccesslevel - en
- Gold
- dc.rights.openaccesslevel - fr
- Or
- dc.rights.uri - en
- https://creativecommons.org/licenses/by-nc-nd/4.0/
- dc.rights.uri - fr
- https://creativecommons.org/licenses/by-nc-nd/4.0/deed.fr
- dc.subject - en
- Health
- dc.subject - fr
- Santé
- dc.subject.en - en
- Health
- dc.subject.fr - fr
- Santé
- dc.title - en
- The Fc-effector function of COVID-19 convalescent plasma contributes to SARS-CoV-2 treatment efficacy in mice
- dc.type - en
- Article
- dc.type - fr
- Article
- local.acceptedmanuscript.articlenum
- 100893
- local.article.journalissue
- 1
- local.article.journaltitle
- Cell Reports Medicine
- local.article.journalvolume
- 4
- local.peerreview - en
- Yes
- local.peerreview - fr
- Oui
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