An ultrapotent pan-β-coronavirus lineage B (β-CoV-B) neutralizing antibody locks the receptor-binding domain in closed conformation by targeting its conserved epitope.
An ultrapotent pan-β-coronavirus lineage B (β-CoV-B) neutralizing antibody locks the receptor-binding domain in closed conformation by targeting its conserved epitope.
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超强泛β冠状病毒谱系 B (β-CoV-B) 中和抗体通过靶向其保守表位将受体结合域锁定在闭合构象中
DOI：
10.1007/s13238-021-00871-6
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发表时间：
2022-09
期刊：
影响因子：
21.1
通讯作者：
Wang Q
中科院分区：
文献类型：
--
作者：
Liu Z;Xu W;Chen Z;Fu W;Zhan W;Gao Y;Zhou J;Zhou Y;Wu J;Wang Q;Zhang X;Hao A;Wu W;Zhang Q;Li Y;Fan K;Chen R;Jiang Q;Mayer CT;Schoofs T;Xie Y;Jiang S;Wen Y;Yuan Z;Wang K;Lu L;Sun L;Wang Q
新出现的SARS-CoV-2流行变异体带来的新威胁突出了寻找治疗性抗体和有效疫苗设计的保守中和表位的必要性。在此，我们鉴定了一种受体结合域（RBD）结合抗体XG 014，其有效中和β-冠状病毒谱系B（β-CoV-B），包括SARS-CoV-2、其循环变体、SARS-CoV和蝙蝠SARS-CoV WIV 1。有趣的是，与XG 014竞争结合的抗体家族成员显示出降低的交叉反应性水平，并诱导抗体依赖性SARS-CoV-2刺突蛋白介导的细胞-细胞融合，这表明XG 014具有独特的识别模式。结构分析表明，XG 014识别ACE 2结合位点外的保守表位，并将RBD完全锁定在非功能性“向下”构象，而其家族成员XG 005直接与ACE 2结合竞争，并将RBD定位“向上”。单次给药XG 014在体内对SARS-CoV-2感染具有保护和治疗作用。我们的研究结果表明，XG 014作为泛-β-CoV-B治疗剂的潜力和XG 014保守抗原表位对于设计针对β-CoV-B和新出现的SARS-CoV-2变体的广泛保护性疫苗的重要性。在线版本包含补充材料，可通过10.1007/s13238-021-00871-6获得。
New threats posed by the emerging circulating variants of SARS-CoV-2 highlight the need to find conserved neutralizing epitopes for therapeutic antibodies and efficient vaccine design. Here, we identified a receptor-binding domain (RBD)-binding antibody, XG014, which potently neutralizes β-coronavirus lineage B (β-CoV-B), including SARS-CoV-2, its circulating variants, SARS-CoV and bat SARSr-CoV WIV1. Interestingly, antibody family members competing with XG014 binding show reduced levels of cross-reactivity and induce antibody-dependent SARS-CoV-2 spike (S) protein-mediated cell-cell fusion, suggesting a unique mode of recognition by XG014. Structural analyses reveal that XG014 recognizes a conserved epitope outside the ACE2 binding site and completely locks RBD in the non-functional “down” conformation, while its family member XG005 directly competes with ACE2 binding and position the RBD “up”. Single administration of XG014 is effective in protection against and therapy of SARS-CoV-2 infection in vivo. Our findings suggest the potential to develop XG014 as pan-β-CoV-B therapeutics and the importance of the XG014 conserved antigenic epitope for designing broadly protective vaccines against β-CoV-B and newly emerging SARS-CoV-2 variants of concern. The online version contains supplementary material available at 10.1007/s13238-021-00871-6.
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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：
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
DOI：
10.4049/jimmunol.2000583
发表时间：
2020-08-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Alsoussi WB;Turner JS;Case JB;Zhao H;Schmitz AJ;Zhou JQ;Chen RE;Lei T;Rizk AA;McIntire KM;Winkler ES;Fox JM;Kafai NM;Thackray LB;Hassan AO;Amanat F;Krammer F;Watson CT;Kleinstein SH;Fremont DH;Diamond MS;Ellebedy AH
通讯作者：
Ellebedy AH
DOI：
10.1016/j.str.2021.05.014
发表时间：
2021-07-01
期刊：
Structure (London, England : 1993)
影响因子：
--
作者：
Cerutti G;Rapp M;Guo Y;Bahna F;Bimela J;Reddem ER;Yu J;Wang P;Liu L;Huang Y;Ho DD;Kwong PD;Sheng Z;Shapiro L
通讯作者：
Shapiro L
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