Mapping mutations to the SARS-CoV-2 RBD that escape binding by different classes of antibodies.
Mapping mutations to the SARS-CoV-2 RBD that escape binding by different classes of antibodies.
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SARS-CoV-2 RBD突变的定位，这些突变逃避了不同类型抗体的结合。
DOI：
10.1038/s41467-021-24435-8
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发表时间：
2021-07-07
影响因子：
16.6
通讯作者：
Bloom JD
中科院分区：
文献类型：
--
作者：
Greaney AJ;Starr TN;Barnes CO;Weisblum Y;Schmidt F;Caskey M;Gaebler C;Cho A;Agudelo M;Finkin S;Wang Z;Poston D;Muecksch F;Hatziioannou T;Bieniasz PD;Robbiani DF;Nussenzweig MC;Bjorkman PJ;Bloom JD
已经从先前感染SARS-CoV-2的个体中分离出针对多种表位的单克隆抗体，但是这些不同抗体类别对多克隆应答的相对贡献仍然不清楚。在这里，我们使用酵母展示系统来映射所有突变的病毒刺突受体结合域（RBD），逃避结合的代表三个有力的中和类抗RBD抗体与高分辨率的结构。我们比较了抗体逃逸地图恢复期多克隆血浆，包括血浆从其中的一些抗体被分离的个人类似的地图。虽然多克隆血浆抗体的结合受到跨多个RBD表位的突变的影响，但血浆逃逸图最类似于靶向RBD上包括位点E484的表位的单类抗体的血浆逃逸图。因此，尽管人类免疫系统可以产生靶向不同RBD表位的抗体，但在实践中，对感染的多克隆应答偏向于靶向已经经历快速进化的表位的单一类别的抗体。新出现的SARS-CoV-2突变体可能逃脱抗体的中和。在这里，作者使用深度突变扫描来识别逃避人类单克隆抗体或恢复期血浆的RBD突变。
Monoclonal antibodies targeting a variety of epitopes have been isolated from individuals previously infected with SARS-CoV-2, but the relative contributions of these different antibody classes to the polyclonal response remains unclear. Here we use a yeast-display system to map all mutations to the viral spike receptor-binding domain (RBD) that escape binding by representatives of three potently neutralizing classes of anti-RBD antibodies with high-resolution structures. We compare the antibody-escape maps to similar maps for convalescent polyclonal plasmas, including plasmas from individuals from whom some of the antibodies were isolated. While the binding of polyclonal plasma antibodies are affected by mutations across multiple RBD epitopes, the plasma-escape maps most resemble those of a single class of antibodies that target an epitope on the RBD that includes site E484. Therefore, although the human immune system can produce antibodies that target diverse RBD epitopes, in practice the polyclonal response to infection is skewed towards a single class of antibodies targeting an epitope that is already undergoing rapid evolution. Emerging SARS-CoV-2 mutants may escape neutralization by antibodies. Here, the authors use deep mutational scanning to identify mutations in the RBD that escape human monoclonal antibodies or convalescent plasmas.
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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
影响因子：
56.9
作者：
Hamilton, SR;Bobrowicz, P;Gerngross, TU
通讯作者：
Gerngross, TU
影响因子：
10.7
作者：
Katoh K;Standley DM
通讯作者：
Standley DM
影响因子：
6.7
作者：
Huang KA;Tan TK;Chen TH;Huang CG;Harvey R;Hussain S;Chen CP;Harding A;Gilbert-Jaramillo J;Liu X;Knight M;Schimanski L;Shih SR;Lin YC;Cheng CY;Cheng SH;Huang YC;Lin TY;Jan JT;Ma C;James W;Daniels RS;McCauley JW;Rijal P;Townsend AR
通讯作者：
Townsend AR