Breadth and function of antibody response to acute SARS-CoV-2 infection in humans.
Breadth and function of antibody response to acute SARS-CoV-2 infection in humans.
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人类急性SARS-CoV-2感染抗体应答的广度和功能。
DOI：
10.1371/journal.ppat.1009352
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发表时间：
2021-03
期刊：
影响因子：
6.7
通讯作者：
Townsend AR
中科院分区：
文献类型：
--
作者：
Huang KA;Tan TK;Chen TH;Huang CG;Harvey R;Hussain S;Chen CP;Harding A;Gilbert-Jaramillo J;Liu X;Knight M;Schimanski L;Shih SR;Lin YC;Cheng CY;Cheng SH;Huang YC;Lin TY;Jan JT;Ma C;James W;Daniels RS;McCauley JW;Rijal P;Townsend AR
我们对三名不同临床严重程度的 COVID-19 患者的血清学和浆母细胞反应以及浆母细胞衍生的 IgG 单克隆抗体 (MAb) 进行了分析。所有患者在发病后 3 周内均检测到有效的体液反应，并且在外周浆母细胞反应后不久或同时引起血清学滴度。平均 13.7% 和 3.5% 的浆母细胞来源的 MAb 分别与病毒刺突糖蛋白或核衣壳发生反应。抗刺突抗体的一个子集（32 种中的 10 种）与测试的其他 β 冠状病毒发生交叉反应，并含有广泛的体细胞突变，表明 SARS-CoV-2 感染后记忆 B 细胞发生扩增。 32 种抗刺突 MAb 中的 14 种，包括 5 种抗受体结合域 (RBD)、3 种抗非 RBD S1 和 6 种抗 S2，在独立测定中中和了野生型 SARS-CoV-2。抗 RBD MAb 进一步分为四个交叉抑制簇，其中来自三个独立簇的六种抗体阻断 RBD 与 ACE2 的结合，五种抗体起到中和作用。所有 ACE2 阻断性抗 RBD 抗体均从两名长期发烧的康复患者中分离出来，这与他们血清中的大量 ACE2 阻断反应相一致。最后，非竞争性中和抗体对的鉴定将为开发针对 SARS-CoV-2 的预防和治疗药物提供潜在的模板。全球COVID-19疫情对人类健康构成严重威胁，抗体介导的免疫在控制人类急性病毒感染方面发挥着关键作用。我们报告了三名不同严重程度的 COVID-19 患者的抗体反应的完整图谱，从血清学到单个浆母细胞衍生的抗体克隆。数据显示，一部分抗刺突浆母细胞衍生抗体与包括人冠状病毒 OC43 在内的其他 β 冠状病毒发生交叉反应，这表明 SARS-CoV-2 感染后记忆 B 细胞会扩张。抗 SARS-CoV-2 刺突抗体克隆靶向刺突糖蛋白的受体结合域 (RBD)、非 RBD S1 和 S2 区域上的多种表位，其中 40% 中和野生型 SARS-CoV-2。抗 RBD 抗体构成中和抗体反应的主要部分。强效抗体靶向 RBD 上的三个非重叠表位，中和活性与 ACE2 结合阻断有关。针对非重叠表位的多个抗体克隆的组合为对抗全球疫情爆发提供了潜在途径。
Serological and plasmablast responses and plasmablast-derived IgG monoclonal antibodies (MAbs) have been analysed in three COVID-19 patients with different clinical severities. Potent humoral responses were detected within 3 weeks of onset of illness in all patients and the serological titre was elicited soon after or concomitantly with peripheral plasmablast response. An average of 13.7% and 3.5% of plasmablast-derived MAbs were reactive with virus spike glycoprotein or nucleocapsid, respectively. A subset of anti-spike (10 of 32) antibodies cross-reacted with other betacoronaviruses tested and harboured extensive somatic mutations, indicative of an expansion of memory B cells upon SARS-CoV-2 infection. Fourteen of 32 anti-spike MAbs, including five anti-receptor-binding domain (RBD), three anti-non-RBD S1 and six anti-S2, neutralised wild-type SARS-CoV-2 in independent assays. Anti-RBD MAbs were further grouped into four cross-inhibiting clusters, of which six antibodies from three separate clusters blocked the binding of RBD to ACE2 and five were neutralising. All ACE2-blocking anti-RBD antibodies were isolated from two recovered patients with prolonged fever, which is compatible with substantial ACE2-blocking response in their sera. Finally, the identification of non-competing pairs of neutralising antibodies would offer potential templates for the development of prophylactic and therapeutic agents against SARS-CoV-2. The global COVID-19 outbreak poses a serious threat to human health and antibody-mediated immunity plays a key role in controlling acute viral infection in humans. We report the complete mapping of antibody responses, from serology through to single plasmablast-derived antibody clone, in three COVID-19 patients with different severities. The data show that a subset of anti-spike plasmablast-derived antibodies cross-react with other betacoronaviruses including human coronavirus OC43, which suggests an expansion of memory B cells upon SARS-CoV-2 infection. Anti-SARS-CoV-2 spike antibody clones target a diverse spectrum of epitopes on the receptor-binding domain (RBD), non-RBD S1 and S2 regions of the spike glycoprotein, 40% of them neutralise wild-type SARS-CoV-2. Anti-RBD antibodies constitute a major part of neutralising antibody response. Potent antibodies target three non-overlapping epitopes on the RBD, and the neutralising activity is linked to ACE2-binding blockade. Combinations of multiple antibody clones targeting non-overlapping epitopes offer a potential avenue to combat the global outbreak.
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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：
4.4
作者：
Lin Y;Gu Y;Wharton SA;Whittaker L;Gregory V;Li X;Metin S;Cattle N;Daniels RS;Hay AJ;McCauley JW
通讯作者：
McCauley JW
影响因子：
7.3
作者：
Fink K
通讯作者：
Fink K
影响因子：
28.3
作者：
Huang, Kuan-Ying A.;Rijal, Pramila;Townsend, Alain R.
通讯作者：
Townsend, Alain R.
影响因子：
82.9
作者：
Long, Quan-Xin;Liu, Bai-Zhong;Huang, Ai-Long
通讯作者：
Huang, Ai-Long