A potently neutralizing SARS-CoV-2 antibody inhibits variants of concern by utilizing unique binding residues in a highly conserved epitope.
A potently neutralizing SARS-CoV-2 antibody inhibits variants of concern by utilizing unique binding residues in a highly conserved epitope.
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DOI：
10.1016/j.immuni.2021.08.016
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发表时间：
2021-10-12
期刊：
影响因子：
32.4
通讯作者：
Diamond MS
中科院分区：
文献类型：
--
作者：
VanBlargan LA;Adams LJ;Liu Z;Chen RE;Gilchuk P;Raju S;Smith BK;Zhao H;Case JB;Winkler ES;Whitener BM;Droit L;Aziati ID;Bricker TL;Joshi A;Shi PY;Creanga A;Pegu A;Handley SA;Wang D;Boon ACM;Crowe JE Jr;Whelan SPJ;Fremont DH;Diamond MS
随着传染性和潜在耐药性增强的严重急性呼吸综合征冠状病毒2 （SARS-CoV-2）变体的出现，需要具有广泛抑制活性的抗体和疫苗。在这里，我们开发了一组中和性抗sars - cov -2单克隆抗体（mab），它们结合刺突蛋白在不同表位的受体结合域，并阻断病毒与其宿主受体人血管紧张素转换酶-2 （hACE2）的附着。虽然一些有效中和的单克隆抗体保护K18-hACE2转基因小鼠免受祖先SARS-CoV-2菌株引起的感染，但其他单克隆抗体在体内诱导逃逸变异或失去对新出现菌株的中和活性。一种单抗SARS2-38能有效中和所有受测的SARS-CoV-2变体，并保护小鼠免受多种SARS-CoV-2毒株的攻击。结构分析表明SARS2-38在受体结合基序的近端有一个保守的表位。因此，使用或诱导结合保守刺突表位的中和抗体进行治疗可能会限制针对新出现的SARS-CoV-2变体的治疗或疫苗效力的丧失。VanBlargan等人描述了一种有效中和的单克隆抗体SARS2-38，它能识别一组SARS-CoV-2变体，并在体内提供治疗保护。结合病毒刺突蛋白的SARS2-38的结构分析揭示了其广泛中和活性的基础，突出了抗体治疗和疫苗设计的表位靶点。
With the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with increased transmissibility and potential resistance, antibodies and vaccines with broadly inhibitory activity are needed. Here, we developed a panel of neutralizing anti-SARS-CoV-2 monoclonal antibodies (mAbs) that bound the receptor binding domain of the spike protein at distinct epitopes and blocked virus attachment to its host receptor, human angiotensin converting enzyme-2 (hACE2). Although several potently neutralizing mAbs protected K18-hACE2 transgenic mice against infection caused by ancestral SARS-CoV-2 strains, others induced escape variants in vivo or lost neutralizing activity against emerging strains. One mAb, SARS2-38, potently neutralized all tested SARS-CoV-2 variants of concern and protected mice against challenge by multiple SARS-CoV-2 strains. Structural analysis showed that SARS2-38 engaged a conserved epitope proximal to the receptor binding motif. Thus, treatment with or induction of neutralizing antibodies that bind conserved spike epitopes may limit the loss of potency of therapies or vaccines against emerging SARS-CoV-2 variants. VanBlargan et al. describe a potently neutralizing mAb, SARS2-38, that recognizes a panel of SARS-CoV-2 variants and confers therapeutic protection in vivo. Structure analysis of SARS2-38 bound to the viral spike protein reveals the basis of its broadly neutralizing activity, highlighting an epitope target for antibody therapeutics and vaccine design.
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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：
10.4049/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：
7.7
作者：
Chen AT;Altschuler K;Zhan SH;Chan YA;Deverman BE
通讯作者：
Deverman BE