High-resolution epitope mapping and characterization of SARS-CoV-2 antibodies in large cohorts of subjects with COVID-19.
High-resolution epitope mapping and characterization of SARS-CoV-2 antibodies in large cohorts of subjects with COVID-19.
复制标题
DOI：
10.1038/s42003-021-02835-2
复制
发表时间：
2021-11-22
影响因子：
5.9
通讯作者：
Shon JC
中科院分区：
文献类型：
--
作者：
Haynes WA;Kamath K;Bozekowski J;Baum-Jones E;Campbell M;Casanovas-Massana A;Daugherty PS;Dela Cruz CS;Dhal A;Farhadian SF;Fitzgibbons L;Fournier J;Jhatro M;Jordan G;Klein J;Lucas C;Kessler D;Luchsinger LL;Martinez B;Catherine Muenker M;Pischel L;Reifert J;Sawyer JR;Waitz R;Wunder EA Jr;Zhang M;Yale IMPACT Team;Iwasaki A;Ko A;Shon JC
随着严重急性呼吸道综合征冠状病毒2型（SARS-CoV-2）的持续传播，对其抗体表位、新出现的毒株、相关冠状病毒，甚至自然感染患者体内的人类蛋白质组进行表征，可以指导有效疫苗和治疗方法的开发。由于传统的表位鉴定工具依赖于预定义的肽序列，因此它们不容易适应于不同的病毒蛋白质组。血清表位库分析（SERA）平台利用高度多样性的随机细菌展示文库来鉴定蛋白质组非依赖性表位结合特异性，然后在感兴趣的生物体的背景下进行分析。当在SARS-CoV-2的背景下评估免疫应答时，我们鉴定了优势表位区域和基序，其表现出将轻度疾病从重度疾病分类并与中和活性相关的潜力。我们强调了与其他冠状病毒交叉反应的SARS-CoV-2表位，并证明了突变型SARS-CoV-2毒株的表位信号降低。总的来说，SARS-CoV-2突变体朝着抗体反应降低的方向进化，突出了数据驱动开发治疗COVID-19的疫苗和疗法的重要性。Haynes、Kamath、Bozekowski等人使用应用于患者血清样品的高通量随机细菌肽展示方法鉴定了引发SARS-CoV-2体液应答的抗原和表位。他们根据疾病的严重程度确定了差异，进一步的计算机分析表明Q677 P的表位信号降低，但D 614 G突变型SARSCoV-2毒株没有。
As Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) continues to spread, characterization of its antibody epitopes, emerging strains, related coronaviruses, and even the human proteome in naturally infected patients can guide the development of effective vaccines and therapies. Since traditional epitope identification tools are dependent upon pre-defined peptide sequences, they are not readily adaptable to diverse viral proteomes. The Serum Epitope Repertoire Analysis (SERA) platform leverages a high diversity random bacterial display library to identify proteome-independent epitope binding specificities which are then analyzed in the context of organisms of interest. When evaluating immune response in the context of SARS-CoV-2, we identify dominant epitope regions and motifs which demonstrate potential to classify mild from severe disease and relate to neutralization activity. We highlight SARS-CoV-2 epitopes that are cross-reactive with other coronaviruses and demonstrate decreased epitope signal for mutant SARS-CoV-2 strains. Collectively, the evolution of SARS-CoV-2 mutants towards reduced antibody response highlight the importance of data-driven development of the vaccines and therapies to treat COVID-19. Using a high throughput, random bacterial peptide display approach applied to patient serum samples, Haynes, Kamath, Bozekowski et al identify the antigens and epitopes that elicit a SARS-CoV-2 humoral response. They identify differences depending on disease severity and further in silico analysis suggests decreased epitope signal for Q677P but not for D614G mutant SARSCoV-2 strains.