Neutralization potency of monoclonal antibodies recognizing dominant and subdominant epitopes on SARS-CoV-2 Spike is impacted by the B.1.1.7 variant.
Neutralization potency of monoclonal antibodies recognizing dominant and subdominant epitopes on SARS-CoV-2 Spike is impacted by the B.1.1.7 variant.
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DOI：
10.1016/j.immuni.2021.03.023
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发表时间：
2021-06-08
期刊：
影响因子：
32.4
通讯作者：
Doores KJ
中科院分区：
文献类型：
--
作者：
Graham C;Seow J;Huettner I;Khan H;Kouphou N;Acors S;Winstone H;Pickering S;Galao RP;Dupont L;Lista MJ;Jimenez-Guardeño JM;Laing AG;Wu Y;Joseph M;Muir L;van Gils MJ;Ng WM;Duyvesteyn HME;Zhao Y;Bowden TA;Shankar-Hari M;Rosa A;Cherepanov P;McCoy LE;Hayday AC;Neil SJD;Malim MH;Doores KJ
SARS-CoV-2刺突受体结合域（RBD）与宿主细胞上的受体ACE 2的相互作用对于病毒进入是必需的。RBD是中和抗体的主要靶标，并且RBD上的几个中和表位已经被分子表征。对传播的SARS-CoV-2变体的分析揭示了在RBD、N-末端结构域（NTD）和Spike的S2亚基中出现的突变。为了了解这些突变如何影响刺突抗原性，我们从SARS-CoV-2感染个体中分离并表征了>100种靶向RBD、NTD和S2上表位的单克隆抗体。约45%显示出中和活性，其中约20%是NTD特异性的。NTD特异性抗体形成两个不同的组：第一个是高度有效的抗感染性病毒，而第二个是不太有效，并显示聚糖依赖性中和活性。B.1.1.7刺突中存在的突变通常赋予对NTD特异性抗体的中和抗性。这项工作表明，在调查新出现的变体中的抗原漂移时，应考虑针对次优势表位的中和抗体。有效的nAbs是从一个无症状的供体分离的，该供体具有低血浆中和性RBD特异性nAbs靶表位与已知的RBD抗体类别重叠，B.1.1.7刺突中的NTD突变赋予对NTD特异性nAbs的中和抗性。大多数RBD特异性nAbs保留了B.1.1.7变体的有效中和作用。SARS-CoV-2刺突中产生的突变对抗原性的影响仍然未知。Graham等从经历一系列COVID-19疾病严重程度的个体中分离出靶向RBD、NTD和非S1表位的有效中和单克隆抗体。所关注的B.1.1.7变体对NTD特异性nAb最具抗性，而RBD特异性nAb保留有效的中和作用。
Interaction of the SARS-CoV-2 Spike receptor binding domain (RBD) with the receptor ACE2 on host cells is essential for viral entry. RBD is the dominant target for neutralizing antibodies, and several neutralizing epitopes on RBD have been molecularly characterized. Analysis of circulating SARS-CoV-2 variants has revealed mutations arising in the RBD, N-terminal domain (NTD) and S2 subunits of Spike. To understand how these mutations affect Spike antigenicity, we isolated and characterized >100 monoclonal antibodies targeting epitopes on RBD, NTD, and S2 from SARS-CoV-2-infected individuals. Approximately 45% showed neutralizing activity, of which ∼20% were NTD specific. NTD-specific antibodies formed two distinct groups: the first was highly potent against infectious virus, whereas the second was less potent and displayed glycan-dependant neutralization activity. Mutations present in B.1.1.7 Spike frequently conferred neutralization resistance to NTD-specific antibodies. This work demonstrates that neutralizing antibodies targeting subdominant epitopes should be considered when investigating antigenic drift in emerging variants. Potent nAbs were isolated from an asymptomatic donor with low plasma neutralization RBD-specific nAbs target epitopes overlapping with known RBD antibody classes NTD mutations in B.1.1.7 Spike confer neutralization resistance to NTD-specific nAbs Most RBD-specific nAbs retain potent neutralization of the B.1.1.7 variant The impact of mutations arising in SARS-CoV-2 Spike on antigenicity is still not known. Graham et al. isolate potent neutralizing monoclonal antibodies from individuals experiencing a range of COVID-19 disease severity that target RBD, NTD, and non-S1 epitopes. The B.1.1.7 variant of concern was most resistant to NTD-specific nAbs whereas RBD-specific nAbs retained potent neutralization.
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影响因子：
5.8
作者：
Gu, Zuguang;Eils, Roland;Schlesner, Matthias
通讯作者：
Schlesner, Matthias
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
影响因子：
17.1
作者：
Kim SI;Noh J;Kim S;Choi Y;Yoo DK;Lee Y;Lee H;Jung J;Kang CK;Song KH;Choe PG;Kim HB;Kim ES;Kim NJ;Seong MW;Park WB;Oh MD;Kwon S;Chung J
通讯作者：
Chung J
SARS-COV-2血统的估计可传播和影响B.1.1.7在英国。
DOI：
10.1126/science.abg3055
发表时间：
2021-04-09
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Davies NG;Abbott S;Barnard RC;Jarvis CI;Kucharski AJ;Munday JD;Pearson CAB;Russell TW;Tully DC;Washburne AD;Wenseleers T;Gimma A;Waites W;Wong KLM;van Zandvoort K;Silverman JD;CMMID COVID-19 Working Group;COVID-19 Genomics UK (COG-UK) Consortium;Diaz-Ordaz K;Keogh R;Eggo RM;Funk S;Jit M;Atkins KE;Edmunds WJ
通讯作者：
Edmunds WJ
影响因子：
6.4
作者：
Guthmiller JJ;Stovicek O;Wang J;Changrob S;Li L;Halfmann P;Zheng NY;Utset H;Stamper CT;Dugan HL;Miller WD;Huang M;Dai YN;Nelson CA;Hall PD;Jansen M;Shanmugarajah K;Donington JS;Krammer F;Fremont DH;Joachimiak A;Kawaoka Y;Tesic V;Madariaga ML;Wilson PC
通讯作者：
Wilson PC