Ladner Jason T, Henson Sierra N, Boyle Annalee S, Engelbrektson Anna L, Fink Zane W, Rahee Fatima, D'ambrozio Jonathan, Schaecher Kurt E, Stone Mars, Dong Wenjuan, Dadwal Sanjeet, Yu Jianhua, Caligiuri Michael A, Cieplak Piotr, Bjørås Magnar, Fenstad Mona H, Nordbø Svein A, Kainov Denis E, Muranaka Norihito, Chee Mark S, Shiryaev Sergey A, Altin John A
The Pathogen and Microbiome Institute, Northern Arizona University, Flagstaff, AZ, USA.
The Translational Genomics Research Institute (TGen), Phoenix and Flagstaff, AZ, USA.
bioRxiv. 2020 Jul 27:2020.07.27.222943. doi: 10.1101/2020.07.27.222943.
A high-resolution understanding of the antibody response to SARS-CoV-2 is important for the design of effective diagnostics, vaccines and therapeutics. However, SARS-CoV-2 antibody epitopes remain largely uncharacterized, and it is unknown whether and how the response may cross-react with related viruses. Here, we use a multiplexed peptide assay ('PepSeq') to generate an epitope-resolved view of reactivity across all human coronaviruses. PepSeq accurately detects SARS-CoV-2 exposure and resolves epitopes across the Spike and Nucleocapsid proteins. Two of these represent recurrent reactivities to conserved, functionally-important sites in the Spike S2 subunit, regions that we show are also targeted for the endemic coronaviruses in pre-pandemic controls. At one of these sites, we demonstrate that the SARS-CoV-2 response strongly and recurrently cross-reacts with the endemic virus hCoV-OC43. Our analyses reveal new diagnostic and therapeutic targets, including a site at which SARS-CoV-2 may recruit common pre-existing antibodies and with the potential for broadly-neutralizing responses.
对严重急性呼吸综合征冠状病毒2（SARS-CoV-2）抗体反应的高分辨率理解对于设计有效的诊断方法、疫苗和治疗方法至关重要。然而，SARS-CoV-2抗体表位在很大程度上仍未得到表征，并且该反应是否以及如何与相关病毒发生交叉反应尚不清楚。在这里，我们使用一种多重肽检测法（“PepSeq”）来生成所有人类冠状病毒反应性的表位解析视图。PepSeq能够准确检测SARS-CoV-2感染情况，并解析刺突蛋白和核衣壳蛋白上的表位。其中两个表位代表对刺突S2亚基中保守的、功能重要位点的反复反应性，我们发现这些区域在大流行前的对照中也是地方性冠状病毒的靶向区域。在其中一个位点，我们证明SARS-CoV-2反应与地方性病毒hCoV-OC43强烈且反复地发生交叉反应。我们的分析揭示了新的诊断和治疗靶点，包括一个SARS-CoV-2可能募集常见的预先存在抗体并具有产生广泛中和反应潜力的位点。
