Discovery of ultrapotent broadly neutralizing antibodies from SARS-CoV-2 elite neutralizers.
Discovery of ultrapotent broadly neutralizing antibodies from SARS-CoV-2 elite neutralizers.
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DOI：
10.1016/j.chom.2021.12.010
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发表时间：
2022-01-12
影响因子：
30.3
通讯作者：
Klein F
中科院分区：
文献类型：
--
作者：
Vanshylla K;Fan C;Wunsch M;Poopalasingam N;Meijers M;Kreer C;Kleipass F;Ruchnewitz D;Ercanoglu MS;Gruell H;Münn F;Pohl K;Janicki H;Nolden T;Bartl S;Stein SC;Augustin M;Dewald F;Gieselmann L;Schommers P;Schulz TF;Sander LE;Koch M;Łuksza M;Lässig M;Bjorkman PJ;Klein F
A fraction of COVID-19 convalescent individuals mount a potent antibody response to SARS-CoV-2 with cross-reactivity to SARS-CoV-1. To uncover their humoral response in detail, we performed single B cell analysis from 10 SARS-CoV-2 elite neutralizers. We isolated and analyzed 126 monoclonal antibodies, many of which were sarbecovirus cross-reactive, with some displaying merbecovirus- and embecovirus-reactivity. Several isolated broadly neutralizing antibodies were effective against B.1.1.7, B.1.351, B.1.429, B.1.617, and B.1.617.2 variants and 19 prominent potential escape sites. Furthermore, assembly of 716,806 SARS-CoV-2 sequences predicted emerging escape variants, which were also effectively neutralized. One of these broadly neutralizing potent antibodies, R40-1G8, is a IGHV3-53 RBD-class-1 antibody. Remarkably, cryo-EM analysis revealed that R40-1G8 has a flexible binding mode, targeting both “up” and “down” conformations of the RBD. Given the threat of emerging SARS-CoV-2 variants, we demonstrate that elite neutralizers are a valuable source for isolating ultrapotent antibody candidates to prevent and treat SARS-CoV-2 infection. Vanshylla et al. deciphered the antibody response in SARS-CoV-2 convalescent elite neutralizers on a single B cell level. Isolated antibodies were highly potent and neutralized various mutants, including the predominant variants of concern and emerging variants. Structural analysis of one potent IGHV3-53/IGKV1-9 bNAb revealed a flexible binding mechanism to the RBD.
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DOI：
10.1056/nejmoa2029849
发表时间：
2021-01-21
期刊：
The New England journal of medicine
影响因子：
--
作者：
Chen P;Nirula A;Heller B;Gottlieb RL;Boscia J;Morris J;Huhn G;Cardona J;Mocherla B;Stosor V;Shawa I;Adams AC;Van Naarden J;Custer KL;Shen L;Durante M;Oakley G;Schade AE;Sabo J;Patel DR;Klekotka P;Skovronsky DM;BLAZE-1 Investigators
通讯作者：
BLAZE-1 Investigators
影响因子：
64.8
作者：
Barnes CO;Jette CA;Abernathy ME;Dam KA;Esswein SR;Gristick HB;Malyutin AG;Sharaf NG;Huey-Tubman KE;Lee YE;Robbiani DF;Nussenzweig MC;West AP Jr;Bjorkman PJ
通讯作者：
Bjorkman PJ
DOI：
10.1056/nejmoa2102685
发表时间：
2021-10-07
期刊：
The New England journal of medicine
影响因子：
--
作者：
Dougan M;Nirula A;Azizad M;Mocherla B;Gottlieb RL;Chen P;Hebert C;Perry R;Boscia J;Heller B;Morris J;Crystal C;Igbinadolor A;Huhn G;Cardona J;Shawa I;Kumar P;Adams AC;Van Naarden J;Custer KL;Durante M;Oakley G;Schade AE;Holzer TR;Ebert PJ;Higgs RE;Kallewaard NL;Sabo J;Patel DR;Dabora MC;Klekotka P;Shen L;Skovronsky DM;BLAZE-1 Investigators
通讯作者：
BLAZE-1 Investigators
影响因子：
64.5
作者：
Dejnirattisai W;Zhou D;Ginn HM;Duyvesteyn HME;Supasa P;Case JB;Zhao Y;Walter TS;Mentzer AJ;Liu C;Wang B;Paesen GC;Slon-Campos J;López-Camacho C;Kafai NM;Bailey AL;Chen RE;Ying B;Thompson C;Bolton J;Fyfe A;Gupta S;Tan TK;Gilbert-Jaramillo J;James W;Knight M;Carroll MW;Skelly D;Dold C;Peng Y;Levin R;Dong T;Pollard AJ;Knight JC;Klenerman P;Temperton N;Hall DR;Williams MA;Paterson NG;Bertram FKR;Siebert CA;Clare DK;Howe A;Radecke J;Song Y;Townsend AR;Huang KA;Fry EE;Mongkolsapaya J;Diamond MS;Ren J;Stuart DI;Screaton GR
通讯作者：
Screaton GR
影响因子：
56.9
作者：
Hsieh, Ching-Lin;Goldsmith, Jory A.;McLellan, Jason S.
通讯作者：
McLellan, Jason S.