Structure-guided T cell vaccine design for SARS-CoV-2 variants and sarbecoviruses.
Structure-guided T cell vaccine design for SARS-CoV-2 variants and sarbecoviruses.
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DOI：
10.1016/j.cell.2021.06.029
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发表时间：
2021-08-19
期刊：
影响因子：
64.5
通讯作者：
Gaiha GD
中科院分区：
文献类型：
--
作者：
Nathan A;Rossin EJ;Kaseke C;Park RJ;Khatri A;Koundakjian D;Urbach JM;Singh NK;Bashirova A;Tano-Menka R;Senjobe F;Waring MT;Piechocka-Trocha A;Garcia-Beltran WF;Iafrate AJ;Naranbhai V;Carrington M;Walker BD;Gaiha GD
严重急性呼吸道综合征冠状病毒2型（SARS-CoV-2）变异体的出现逃避了恢复期和疫苗诱导的抗体反应，重新关注广泛保护性T细胞疫苗的开发。在这里，我们应用基于结构的网络分析和评估HLA I类肽的稳定性，以确定突变限制的CD 8 + T细胞表位的SARS-CoV-2蛋白质组。高度网络化的残基在循环变体和肉瘤病毒中是暂时保守的，并且在突变时不成比例地损害刺突假型慢病毒的感染性。对18个全球流行等位基因的HLA I类稳定活性的评估确定了在循环SARS-CoV-2变体和深度测序的原代分离株中具有有限突变频率的高度网络化区域内的CD 8 + T细胞表位。此外，这些表位在恢复期个体中引起可证实的CD 8 + T细胞反应性，但在基于mRNA的疫苗的接受者中降低识别。因此，这些数据阐明了SARS-CoV-2蛋白质组中的关键突变限制区域和免疫原性表位，用于针对新出现的变体和SARS样冠状病毒的全球T细胞疫苗。基于结构的网络分析确定了SARS-CoV-2蛋白质组中受突变限制的区域，这些区域携带在新出现的变体以及其他肉瘤病毒中也保守的CD 8 + T细胞表位。这些表位在恢复期个体中引起比mRNA疫苗接受者更强的CD 8 + T细胞应答，并为针对冠状病毒的广泛的基于T细胞的疫苗提供框架。
The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants that escape convalescent and vaccine-induced antibody responses has renewed focus on the development of broadly protective T-cell-based vaccines. Here, we apply structure-based network analysis and assessments of HLA class I peptide stability to define mutationally constrained CD8+ T cell epitopes across the SARS-CoV-2 proteome. Highly networked residues are conserved temporally among circulating variants and sarbecoviruses and disproportionately impair spike pseudotyped lentivirus infectivity when mutated. Evaluation of HLA class I stabilizing activity for 18 globally prevalent alleles identifies CD8+ T cell epitopes within highly networked regions with limited mutational frequencies in circulating SARS-CoV-2 variants and deep-sequenced primary isolates. Moreover, these epitopes elicit demonstrable CD8+ T cell reactivity in convalescent individuals but reduced recognition in recipients of mRNA-based vaccines. These data thereby elucidate key mutationally constrained regions and immunogenic epitopes in the SARS-CoV-2 proteome for a global T-cell-based vaccine against emerging variants and SARS-like coronaviruses. Structure-based network analyses identify regions in the SARS-CoV-2 proteome that are mutationally constrained and bear CD8+ T cell epitopes that are also conserved in emerging variants as well as other sarbecoviruses. These epitopes elicit stronger CD8+ T cell responses in convalescent individuals over mRNA vaccine recipients and provide a framework for a broad T-cell-based vaccine against coronaviruses.
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DOI：
10.1126/science.abg3055
发表时间：
2021-04-09
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Davies NG;Abbott S;Barnard RC;Jarvis CI;Kucharski AJ;Munday JD;Pearson CAB;Russell TW;Tully DC;Washburne AD;Wenseleers T;Gimma A;Waites W;Wong KLM;van Zandvoort K;Silverman JD;CMMID COVID-19 Working Group;COVID-19 Genomics UK (COG-UK) Consortium;Diaz-Ordaz K;Keogh R;Eggo RM;Funk S;Jit M;Atkins KE;Edmunds WJ
通讯作者：
Edmunds WJ
影响因子：
32.4
作者：
Ferretti AP;Kula T;Wang Y;Nguyen DMV;Weinheimer A;Dunlap GS;Xu Q;Nabilsi N;Perullo CR;Cristofaro AW;Whitton HJ;Virbasius A;Olivier KJ Jr;Buckner LR;Alistar AT;Whitman ED;Bertino SA;Chattopadhyay S;MacBeath G
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MacBeath G
影响因子：
158.5
作者：
Keech, Cheryl;Albert, Gary;Glenn, Gregory M.
通讯作者：
Glenn, Gregory M.
DOI：
10.1056/nejmoa2035389
发表时间：
2021-02-04
期刊：
The New England journal of medicine
影响因子：
--
作者：
Baden LR;El Sahly HM;Essink B;Kotloff K;Frey S;Novak R;Diemert D;Spector SA;Rouphael N;Creech CB;McGettigan J;Khetan S;Segall N;Solis J;Brosz A;Fierro C;Schwartz H;Neuzil K;Corey L;Gilbert P;Janes H;Follmann D;Marovich M;Mascola J;Polakowski L;Ledgerwood J;Graham BS;Bennett H;Pajon R;Knightly C;Leav B;Deng W;Zhou H;Han S;Ivarsson M;Miller J;Zaks T;COVE Study Group
通讯作者：
COVE Study Group
影响因子：
8.8
作者：
Hoffmann M;Zhang L;Krüger N;Graichen L;Kleine-Weber H;Hofmann-Winkler H;Kempf A;Nessler S;Riggert J;Winkler MS;Schulz S;Jäck HM;Pöhlmann S
通讯作者：
Pöhlmann S