Broadly neutralizing antibodies overcome SARS-CoV-2 Omicron antigenic shift.
Broadly neutralizing antibodies overcome SARS-CoV-2 Omicron antigenic shift.
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DOI：
10.1038/s41586-021-04386-2
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发表时间：
2022-02
期刊：
影响因子：
64.8
通讯作者：
中科院分区：
文献类型：
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作者：
最近出现的SARS-CoV-2 Omicron变异株编码了SPEKE(S)蛋白中的37个氨基酸替换，其中15个位于受体结合域，从而引起了人们对现有疫苗和抗体疗法有效性的担忧。在这里，我们发现，相对于武汉-HU-1 RBD，Omicron RBD与人ACE2结合的亲和力增强，并与小鼠ACE2结合。在恢复期和疫苗接种的个体中，与祖先的假病毒相比，针对奥美康的血浆中和活性显著降低，但在第三次疫苗接种后，这种损失不那么明显。大多数受体结合基序(RBM)导向的单抗在体外失去了对奥美康的中和活性，29株单抗中只有3株保持了不变的效力，包括模拟ACE2的S2K146单抗。此外，部分广泛中和的肉瘤病毒单抗通过识别RBM外的抗原位点而中和Omicron，包括Sotrovimab、S2X259和S2H97。奥米克介导的免疫逃避的规模标志着SARS-CoV-2抗原性的重大转变。识别SARS-CoV-2变异体和其他肉瘤病毒之间保守的RBD表位的广泛中和单抗可能被证明是控制正在进行的大流行和未来人畜共患病溢出的关键。
The recently emerged SARS-CoV-2 Omicron variant encodes 37 amino acid substitutions in the spike (S) protein, 15 of which are in the receptor-binding domain (RBD), thereby raising concerns about the effectiveness of available vaccines and antibody therapeutics. Here, we show that the Omicron RBD binds to human ACE2 with enhanced affinity, relative to the Wuhan-Hu-1 RBD, and binds to mouse ACE2. Marked reductions of plasma neutralizing activity were observed against Omicron compared to the ancestral pseudovirus for convalescent and vaccinated individuals, but this loss was less pronounced after a third vaccine dose. Most receptor-binding motif (RBM)-directed monoclonal antibodies (mAbs) lost in vitro neutralizing activity against Omicron, with only 3 out of 29 mAbs retaining unaltered potency, including the ACE2-mimicking S2K146 mAb. Furthermore, a fraction of broadly neutralizing sarbecovirus mAbs neutralized Omicron through recognition of antigenic sites outside the RBM, including sotrovimab, S2X259 and S2H97. The magnitude of Omicron-mediated immune evasion marks a major SARS-CoV-2 antigenic shift. Broadly neutralizing mAbs recognizing RBD epitopes conserved among SARS-CoV-2 variants and other sarbecoviruses may prove key to controlling the ongoing pandemic and future zoonotic spillovers.
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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：
7.3
作者：
Bergström JJ;Xu H;Heyman B
通讯作者：
Heyman B
影响因子：
17.1
作者：
Jones BE;Brown-Augsburger PL;Corbett KS;Westendorf K;Davies J;Cujec TP;Wiethoff CM;Blackbourne JL;Heinz BA;Foster D;Higgs RE;Balasubramaniam D;Wang L;Zhang Y;Yang ES;Bidshahri R;Kraft L;Hwang Y;Žentelis S;Jepson KR;Goya R;Smith MA;Collins DW;Hinshaw SJ;Tycho SA;Pellacani D;Xiang P;Muthuraman K;Sobhanifar S;Piper MH;Triana FJ;Hendle J;Pustilnik A;Adams AC;Berens SJ;Baric RS;Martinez DR;Cross RW;Geisbert TW;Borisevich V;Abiona O;Belli HM;de Vries M;Mohamed A;Dittmann M;Samanovic MI;Mulligan MJ;Goldsmith JA;Hsieh CL;Johnson NV;Wrapp D;McLellan JS;Barnhart BC;Graham BS;Mascola JR;Hansen CL;Falconer E
通讯作者：
Falconer E
REGN-COV2抗体预防和治疗恒河猕猴和仓鼠中的SARS-COV-2感染。
DOI：
10.1126/science.abe2402
发表时间：
2020-11-27
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Baum A;Ajithdoss D;Copin R;Zhou A;Lanza K;Negron N;Ni M;Wei Y;Mohammadi K;Musser B;Atwal GS;Oyejide A;Goez-Gazi Y;Dutton J;Clemmons E;Staples HM;Bartley C;Klaffke B;Alfson K;Gazi M;Gonzalez O;Dick E Jr;Carrion R Jr;Pessaint L;Porto M;Cook A;Brown R;Ali V;Greenhouse J;Taylor T;Andersen H;Lewis MG;Stahl N;Murphy AJ;Yancopoulos GD;Kyratsous CA
通讯作者：
Kyratsous CA
影响因子：
64.5
作者：
Corti D;Purcell LA;Snell G;Veesler D
通讯作者：
Veesler D