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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DOI：
10.1016/j.xcrm.2022.100893
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发表时间：
2023-01-17
影响因子：
14.3
通讯作者：
Uchil, Pradeep D.
中科院分区：
文献类型：
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作者：
Ullah, Irfan;Beaudoin-Bussieres, Guillaume;Symmes, Kelly;Cloutier, Marc;Ducas, Eric;Tauzin, Alexandra;Laumaea, Annemarie;Grunst, Michael W.;Dionne, Katrina;Richard, Jonathan;Begin, Philippe;Mothes, Walther;Kumar, Priti;Bazin, Renee;Finzi, Andres;Uchil, Pradeep D.
根据中和滴度和抗刺免疫球蛋白水平选择新冠肺炎恢复期血浆(CCP)进行血浆治疗。然而，促进SARS-CoV-2控制的CCP特征是复杂的和不完全定义的。使用体内成像方法，我们证明了低中和(ID_(50)：≤1：250)，但中等到高FC效应活性的CCP，与那些FC功能较差的CCP相比，可以延迟死亡和/或提高K18-hACE2攻击小鼠的存活率。天然免疫细胞对CCP疗效的影响取决于其残留的中和活性。对所选CCP的分级显示，治疗期间需要免疫球蛋白和免疫球蛋白(M+A)，但在预防期间仅有免疫球蛋白部分就足够了。最后，尽管降低了中和作用，但祖先SARS-CoV-2诱导的CCP显著延迟了Delta和Beta诱导的死亡率，这表明Fc效应功能有助于对VOCs的免疫。因此，CCP的Fc活性在中和受损时提供了第二道防线，可以作为CCP选择的重要标准。新冠肺炎恢复期血浆(CCP)具有强大的FC功能，可以保护小鼠的FC功能，当中和能力受损时，CCP的活性可以作为二次防御，Fc功能可以促进针对SARS-CoV-2变异株的交叉反应免疫，FC功能可以作为选择CCP用于治疗SARS-CoV-2的关键参数之一。在这里，Ullah等人。结果表明，具有低中和活性但Fc功能强大的CCP可以延缓SARS-CoV-2诱导的疾病进展，并促进针对所关注变种的交叉反应免疫，提示Fc功能可以区分CCPs用于治疗用途。
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. 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 SARS-CoV-2 control by COVID-19 convalescent plasmas (CCPs) is complex and poorly understood. Here Ullah et al. show that CCPs with low neutralizing activity but robust Fc function can delay SARS-CoV-2-induced disease progression and promote cross-reactive immunity against variants of concern, suggesting that Fc functions can demarcate CCPs for therapeutic use.
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DOI：
10.1016/j.xcrm.2021.100290
发表时间：
2021-06-15
期刊：
Cell reports. Medicine
影响因子：
--
作者：
Anand SP;Prévost J;Nayrac M;Beaudoin-Bussières G;Benlarbi M;Gasser R;Brassard N;Laumaea A;Gong SY;Bourassa C;Brunet-Ratnasingham E;Medjahed H;Gendron-Lepage G;Goyette G;Gokool L;Morrisseau C;Bégin P;Martel-Laferrière V;Tremblay C;Richard J;Bazin R;Duerr R;Kaufmann DE;Finzi A
通讯作者：
Finzi A
FC工程方法定义了针对埃博拉病毒的免疫力的功能体液相关性。
影响因子：
32.4
作者：
Gunn BM;Lu R;Slein MD;Ilinykh PA;Huang K;Atyeo C;Schendel SL;Kim J;Cain C;Roy V;Suscovich TJ;Takada A;Halfmann PJ;Kawaoka Y;Pauthner MG;Momoh M;Goba A;Kanneh L;Andersen KG;Schieffelin JS;Grant D;Garry RF;Saphire EO;Bukreyev A;Alter G
通讯作者：
Alter G
DOI：
10.1056/nejmoa2103784
发表时间：
2021-11-18
期刊：
The New England journal of medicine
影响因子：
--
作者：
Korley FK;Durkalski-Mauldin V;Yeatts SD;Schulman K;Davenport RD;Dumont LJ;El Kassar N;Foster LD;Hah JM;Jaiswal S;Kaplan A;Lowell E;McDyer JF;Quinn J;Triulzi DJ;Van Huysen C;Stevenson VLW;Yadav K;Jones CW;Kea B;Burnett A;Reynolds JC;Greineder CF;Haas NL;Beiser DG;Silbergleit R;Barsan W;Callaway CW;SIREN-C3PO Investigators
通讯作者：
SIREN-C3PO Investigators
影响因子：
4.2
作者：
Gundlapalli AV;Salerno RM;Brooks JT;Averhoff F;Petersen LR;McDonald LC;Iademarco MF;CDC COVID-19 Response
通讯作者：
CDC COVID-19 Response
影响因子：
17.1
作者：
Kaplonek P;Cizmeci D;Fischinger S;Collier AR;Suscovich T;Linde C;Broge T;Mann C;Amanat F;Dayal D;Rhee J;de St Aubin M;Nilles EJ;Musk ER;Menon AS;Saphire EO;Krammer F;Lauffenburger DA;Barouch DH;Alter G
通讯作者：
Alter G