A Fc-enhanced NTD-binding non-neutralizing antibody delays virus spread and synergizes with a nAb to protect mice from lethal SARS-CoV-2 infection.
A Fc-enhanced NTD-binding non-neutralizing antibody delays virus spread and synergizes with a nAb to protect mice from lethal SARS-CoV-2 infection.
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DOI：
10.1016/j.celrep.2022.110368
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发表时间：
2022-02-15
期刊：
影响因子：
8.8
通讯作者：
Finzi A
中科院分区：
文献类型：
--
作者：
Beaudoin-Bussières G;Chen Y;Ullah I;Prévost J;Tolbert WD;Symmes K;Ding S;Benlarbi M;Gong SY;Tauzin A;Gasser R;Chatterjee D;Vézina D;Goyette G;Richard J;Zhou F;Stamatatos L;McGuire AT;Charest H;Roger M;Pozharski E;Kumar P;Mothes W;Uchil PD;Pazgier M;Finzi A
新出现的证据表明，抗体的中和和Fc介导的效应子功能有助于保护免受SARS-CoV-2的侵害。目前尚不清楚Fc效应子功能是否可以单独保护SARS-CoV-2。在这里，我们分离出CV 3 -13，一种非中和抗体，从一个恢复期的个人与强大的Fc介导的效应功能。CV 3 -13与SARS-CoV-2刺突复合物的冷冻电子显微镜结构显示，抗体从不同的接近角度结合到N-末端结构域（NTD）表位，该表位仅与中和抗体识别的NTD超位点部分重叠。CV 3 -13不改变SARS-CoV-2在K18-hACE 2小鼠中的复制动力学，但其Fc增强型在预防性环境中显著延迟病毒传播、神经侵袭和死亡。有趣的是，Fc增强的非中和性CV 3 -13与Fc受损的中和性CV 3 -25的组合完全保护小鼠免受致死性SARS-CoV-2感染。总之，我们的数据表明，有效的Fc介导的效应子功能可以有力地促进抗SARS-CoV-2抗体的体内功效。非nAb对SARS-CoV-2感染的体内影响尚不清楚。在这里，Beaudoin-Bussières等人。显示Fc增强型非nAb CV 3 -13延迟SARS-CoV-2在小鼠中的传播和死亡。Fc增强的CV 3 -13与Fc受损的nAb组合协同保护小鼠，揭示了非nAb在SARS-CoV-2感染期间的重要性。
Emerging evidence indicates that both neutralizing and Fc-mediated effector functions of antibodies contribute to protection against SARS-CoV-2. It is unclear whether Fc-effector functions alone can protect against SARS-CoV-2. Here, we isolated CV3-13, a non-neutralizing antibody, from a convalescent individual with potent Fc-mediated effector functions. The cryoelectron microscopy structure of CV3-13 in complex with the SARS-CoV-2 spike reveals that the antibody binds from a distinct angle of approach to an N-terminal domain (NTD) epitope that only partially overlaps with the NTD supersite recognized by neutralizing antibodies. CV3-13 does not alter the replication dynamics of SARS-CoV-2 in K18-hACE2 mice, but its Fc-enhanced version significantly delays virus spread, neuroinvasion, and death in prophylactic settings. Interestingly, the combination of Fc-enhanced non-neutralizing CV3-13 with Fc-compromised neutralizing CV3-25 completely protects mice from lethal SARS-CoV-2 infection. Altogether, our data demonstrate that efficient Fc-mediated effector functions can potently contribute to the in vivo efficacy of anti-SARS-CoV-2 antibodies. The in vivo impact of non-nAbs on SARS-CoV-2 infection is unclear. Here, Beaudoin-Bussières et al. show that a Fc-enhanced version of non-nAb CV3-13 delays SARS-CoV-2 spread and death in mice. Fc-enhanced CV3-13 combined with a Fc-compromised nAb synergizes to protect mice, revealing the importance of non-nAbs during SARS-CoV-2 infection.
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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
影响因子：
14.9
作者：
Dunbar J;Krawczyk K;Leem J;Marks C;Nowak J;Regep C;Georges G;Kelm S;Popovic B;Deane CM
通讯作者：
Deane CM
影响因子：
48
作者：
Barad BA;Echols N;Wang RY;Cheng Y;DiMaio F;Adams PD;Fraser JS
通讯作者：
Fraser JS
DOI：
10.1107/s0907444904019158
发表时间：
2004-12-01
影响因子：
2.2
作者：
Emsley, P;Cowtan, K
通讯作者：
Cowtan, K
影响因子：
5.4
作者：
Acharya, Priyamvada;Tolbert, William D.;Pazgier, Marzena
通讯作者：
Pazgier, Marzena