Omicron escapes the majority of existing SARS-CoV-2 neutralizing antibodies.
Omicron escapes the majority of existing SARS-CoV-2 neutralizing antibodies.
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DOI：
10.1038/s41586-021-04385-3
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发表时间：
2022-03
期刊：
影响因子：
64.8
通讯作者：
Xie XS
中科院分区：
文献类型：
--
作者：
Cao Y;Wang J;Jian F;Xiao T;Song W;Yisimayi A;Huang W;Li Q;Wang P;An R;Wang J;Wang Y;Niu X;Yang S;Liang H;Sun H;Li T;Yu Y;Cui Q;Liu S;Yang X;Du S;Zhang Z;Hao X;Shao F;Jin R;Wang X;Xiao J;Wang Y;Xie XS
SARS-CoV-2 B.1.1.529（Omicron）变体包含受体结合域（RBD）的15个突变。Omicron如何逃避RBD靶向中和抗体需要立即调查。在这里，我们使用高通量酵母展示筛选来确定247种人抗RBD中和抗体的RBD逃逸突变的概况，并表明中和抗体可以通过无监督聚类分为六个表位组（A-F）-这一分组与基于知识的结构分类高度一致。Omicron的各种单一突变可损害不同表位组的中和抗体。具体地，A-D组中的中和抗体（其表位与ACE 2结合基序重叠）在很大程度上被K417 N、G446 S、E484 A和Q493 R逃逸。E组（例如，S309）和F组（例如，CR 3022）中的抗体通常表现出广泛的肉瘤病毒中和活性，受Omicron的影响较小，但G339 D、N440 K和S371 L仍然逃避了一部分中和抗体。此外，Omicron假病毒中和表明，由于其表位上的多个协同突变，维持单个突变的中和抗体也可以逃逸。总的来说，超过85%的检测中和抗体被Omicron逃逸。关于基于中和抗体的药物，LY-CoV 016、LY-CoV 555、REGN 10933、REGN 10987、AZD 1061、AZD 8895和BRII-196的中和效力被Omicron大大削弱，而VIR-7831和DXP-604的有效性仍然降低。总之，我们的数据表明，感染Omicron将导致相当大的体液免疫逃避，中和抗体靶向的Sarbecovirus保守区将保持最有效。我们的研究结果为开发针对Omicron和未来变体的抗体药物和疫苗提供了信息。高通量酵母展示平台用于分析SARS-CoV-2受体结合结构域（RBD）中的突变概况，这些突变能够逃避抗体，并表明大多数抗RBD抗体可以被Omicron变体逃避。
The SARS-CoV-2 B.1.1.529 (Omicron) variant contains 15 mutations of the receptor-binding domain (RBD). How Omicron evades RBD-targeted neutralizing antibodies requires immediate investigation. Here we use high-throughput yeast display screening to determine the profiles of RBD escaping mutations for 247 human anti-RBD neutralizing antibodies and show that the neutralizing antibodies can be classified by unsupervised clustering into six epitope groups (A–F)—a grouping that is highly concordant with knowledge-based structural classifications. Various single mutations of Omicron can impair neutralizing antibodies of different epitope groups. Specifically, neutralizing antibodies in groups A–D, the epitopes of which overlap with the ACE2-binding motif, are largely escaped by K417N, G446S, E484A and Q493R. Antibodies in group E (for example, S309) and group F (for example, CR3022), which often exhibit broad sarbecovirus neutralizing activity, are less affected by Omicron, but a subset of neutralizing antibodies are still escaped by G339D, N440K and S371L. Furthermore, Omicron pseudovirus neutralization showed that neutralizing antibodies that sustained single mutations could also be escaped, owing to multiple synergetic mutations on their epitopes. In total, over 85% of the tested neutralizing antibodies were escaped by Omicron. With regard to neutralizing-antibody-based drugs, the neutralization potency of LY-CoV016, LY-CoV555, REGN10933, REGN10987, AZD1061, AZD8895 and BRII-196 was greatly undermined by Omicron, whereas VIR-7831 and DXP-604 still functioned at a reduced efficacy. Together, our data suggest that infection with Omicron would result in considerable humoral immune evasion, and that neutralizing antibodies targeting the sarbecovirus conserved region will remain most effective. Our results inform the development of antibody-based drugs and vaccines against Omicron and future variants. A high-throughput yeast display platform is used to analyse the profiles of mutations in the SARS-CoV-2 receptor-binding domain (RBD) that enable escape from antibodies, and suggests that most anti-RBD antibodies can be escaped by the Omicron variant.
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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：
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
DOI：
10.1126/science.abc4730
发表时间：
2020-09-25
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Gu H;Chen Q;Yang G;He L;Fan H;Deng YQ;Wang Y;Teng Y;Zhao Z;Cui Y;Li Y;Li XF;Li J;Zhang NN;Yang X;Chen S;Guo Y;Zhao G;Wang X;Luo DY;Wang H;Yang X;Li Y;Han G;He Y;Zhou X;Geng S;Sheng X;Jiang S;Sun S;Qin CF;Zhou Y
通讯作者：
Zhou Y
影响因子：
64.5
作者：
Li Q;Nie J;Wu J;Zhang L;Ding R;Wang H;Zhang Y;Li T;Liu S;Zhang M;Zhao C;Liu H;Nie L;Qin H;Wang M;Lu Q;Li X;Liu J;Liang H;Shi Y;Shen Y;Xie L;Zhang L;Qu X;Xu W;Huang W;Wang Y
通讯作者：
Wang Y
两种抗体鸡尾酒中和中和的遗传和结构基础。
影响因子：
28.3
作者：
Dong J;Zost SJ;Greaney AJ;Starr TN;Dingens AS;Chen EC;Chen RE;Case JB;Sutton RE;Gilchuk P;Rodriguez J;Armstrong E;Gainza C;Nargi RS;Binshtein E;Xie X;Zhang X;Shi PY;Logue J;Weston S;McGrath ME;Frieman MB;Brady T;Tuffy KM;Bright H;Loo YM;McTamney PM;Esser MT;Carnahan RH;Diamond MS;Bloom JD;Crowe JE Jr
通讯作者：
Crowe JE Jr