Rational identification of potent and broad sarbecovirus-neutralizing antibody cocktails from SARS convalescents.
Rational identification of potent and broad sarbecovirus-neutralizing antibody cocktails from SARS convalescents.
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DOI：
10.1016/j.celrep.2022.111845
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发表时间：
2022-12-20
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影响因子：
8.8
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中科院分区：
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严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) Omicron 亚系已经逃脱了大多数靶向受体结合域 (RBD) 的治疗性中和抗体 (NAb)，这证明之前的 NAb 药物筛选策略对于快速进化的 SARS-CoV-2 存在缺陷。需要更广泛的 Nab 候选药物选择方法。在这里，我们描述了一种合理的方法来识别 RBD 靶向广泛的 SARS-CoV-2 NAb 混合物。基于高通量表位测定，我们建议广泛的 NAb 药物应靶向非免疫显性 RBD 表位，以避免群体免疫导向的逃逸突变。此外，它们的相互作用的抗原残基应该集中在sarbecovirus保守位点并与关键的病毒功能相关，从而使得抗体逃逸突变不太可能出现。根据这些标准，从接种 SARS-CoV-2 的 SARS 康复者中分离出的大量广泛 sarbecovirus NAb 中鉴定出一种特色非竞争性抗体混合物 SA55+SA58。 SA55+SA58 可有效中和利用 ACE2 的 sarbecovirus，包括循环的 Omicron 变种，并可作为广泛的 SARS-CoV-2 预防剂，提供长期保护，特别是对于免疫功能低下或患有高危合并症的个体。曹等人。描述了一种利用高通量表位作图来识别广泛的 sarbecovirus 中和抗体混合物的策略，该抗体混合物对于未来的 SARS-CoV-2 变体来说很难逃脱。由此产生的抗体混合物，名为 SA55+SA58，对利用 ACE2 的 sarbecoviruses 表现出高中和效力和广度，并有效保护小鼠免受 BA.1 和 BA.5 感染。
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron sublineages have escaped most receptor-binding domain (RBD)-targeting therapeutic neutralizing antibodies (NAbs), which proves that previous NAb drug screening strategies are deficient against the fast-evolving SARS-CoV-2. Better broad NAb drug candidate selection methods are needed. Here, we describe a rational approach for identifying RBD-targeting broad SARS-CoV-2 NAb cocktails. Based on high-throughput epitope determination, we propose that broad NAb drugs should target non-immunodominant RBD epitopes to avoid herd-immunity-directed escape mutations. Also, their interacting antigen residues should focus on sarbecovirus conserved sites and associate with critical viral functions, making the antibody-escaping mutations less likely to appear. Following these criteria, a featured non-competing antibody cocktail, SA55+SA58, is identified from a large collection of broad sarbecovirus NAbs isolated from SARS-CoV-2-vaccinated SARS convalescents. SA55+SA58 potently neutralizes ACE2-utilizing sarbecoviruses, including circulating Omicron variants, and could serve as broad SARS-CoV-2 prophylactics to offer long-term protection, especially for individuals who are immunocompromised or with high-risk comorbidities. Cao et al. describe a strategy to identify a broad sarbecovirus-neutralizing antibody cocktail that would be hard to escape for future SARS-CoV-2 variants using high-throughput epitope mapping. The resulting antibody cocktail, named SA55+SA58, exhibits high neutralizing potency and breadth against ACE2-utilizing sarbecoviruses and efficiently protects mice from BA.1 and BA.5 infection.
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影响因子：
30.5
作者：
He, Wan-ting;Musharrafieh, Rami;Song, Ge;Dueker, Katharina;Tse, Longping V.;Martinez, David R.;Schafer, Alexandra;Callaghan, Sean;Yong, Peter;Beutler, Nathan;Torres, Jonathan L.;Volk, Reid M.;Zhou, Panpan;Yuan, Meng;Liu, Hejun;Anzanello, Fabio;Capozzola, Tazio;Parren, Mara;Garcia, Elijah;Rawlings, Stephen A.;Smith, Davey M.;Wilson, Ian A.;Safonova, Yana;Ward, Andrew B.;Rogers, Thomas F.;Baric, Ralph S.;Gralinski, Lisa E.;Burton, Dennis R.;Andrabi, Raiees
通讯作者：
Andrabi, Raiees
影响因子：
64.8
作者：
Cao, Yunlong;Yisimayi, Ayijiang;Jian, Fanchong;Song, Weiliang;Xiao, Tianhe;Wang, Lei;Du, Shuo;Wang, Jing;Li, Qianqian;Chen, Xiaosu;Yu, Yuanling;Wang, Peng;Zhang, Zhiying;Liu, Pulan;An, Ran;Hao, Xiaohua;Wang, Yao;Feng, Rui;Sun, Haiyan;Zhao, Lijuan;Zhang, Wen;Zhao, Dong;Zheng, Jiang;Yu, Lingling;Li, Can;Zhang, Na;Wang, Rui;Niu, Xiao;Yang, Sijie;Song, Xuetao;Chai, Yangyang;Hu, Ye;Shi, Yansong;Zheng, Linlin;Li, Zhiqiang;Gu, Qingqing;Shao, Fei;Huang, Weijin;Jin, Ronghua;Shen, Zhongyang;Wang, Youchun;Wang, Xiangxi;Xiao, Junyu;Xie, Xiaoliang Sunney
通讯作者：
Xie, Xiaoliang Sunney
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
DOI：
10.1126/science.abq3773
发表时间：
2022-08-12
期刊：
Science (New York, N.Y.)
影响因子：
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影响因子：
13.2
作者：
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