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Published December 29, 2022
DOI: https://doi.org/10.1016/j.xcrm.2022.100893
Irfan Ullah Guillaume Beaudoin-Bussières 11 Kelly Symmes 11 Renée Bazin Andrés Finzi 10 Pradeep D. Uchil 8, 9, 12 Show all authors
Highlights
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.
DOI: https://doi.org/10.1016/j.xcrm.2022.100893
Irfan Ullah Guillaume Beaudoin-Bussières 11 Kelly Symmes 11 Renée Bazin Andrés Finzi 10 Pradeep D. Uchil 8, 9, 12 Show all authors
Highlights
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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
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.