Stereotypic neutralizing V(H) antibodies against SARS-CoV-2 spike protein receptor binding domain in patients with COVID-19 and healthy individuals.
Stereotypic neutralizing V(H) antibodies against SARS-CoV-2 spike protein receptor binding domain in patients with COVID-19 and healthy individuals.
复制标题
DOI：
10.1126/scitranslmed.abd6990
复制
发表时间：
2021-01-27
影响因子：
17.1
通讯作者：
Chung J
中科院分区：
文献类型：
--
作者：
Kim SI;Noh J;Kim S;Choi Y;Yoo DK;Lee Y;Lee H;Jung J;Kang CK;Song KH;Choe PG;Kim HB;Kim ES;Kim NJ;Seong MW;Park WB;Oh MD;Kwon S;Chung J
COVID-19 患者和健康个体中针对 SARS-CoV-2 受体结合域的刻板型中和抗体克隆型。健康个体中预先存在的未经历体细胞超突变或类别转换的幼稚 B 细胞会产生定型抗体 (Abs)。金等人。在健康个体和 COVID-19 患者中鉴定出针对 SARS-CoV-2 刺突蛋白受体结合域 (RBD) 的定型中和抗体 (nAb)。他们在 17 名 COVID-19 患者中的 13 名中检测到了由 Ig 重链可变 3-53 (IGHV3-53) 或 IGHV3-66 和 Ig 重链连接 6 (IGHJ6) 基因组成的 RBD 特异性定型可变重链 (VH) Ab 克隆型。一种定型 nAb 可以抑制 SARS-CoV-2 临床分离株的体外复制。这些 VH 克隆型也在 10 名没有接触过 SARS-CoV-2 证据的健康个体中的 6 名中发现，这些发现共同提供了存在预先存在的 SARS-CoV-2 nAb 的证据。定型抗体克隆型存在于健康个体中，并且可以通过中和提供针对病毒感染的保护性免疫力。我们观察到 17 名 COVID-19 患者中有 13 名具有针对 SARS-CoV-2 刺突蛋白受体结合域 (RBD) 的刻板可变重链 (VH) 抗体克隆型。这些抗体克隆型由免疫球蛋白重链可变区 3-53 (IGHV3-53) 或 IGHV3-66 和免疫球蛋白重链连接 6 (IGHJ6) 基因组成。这些克隆型包括 IgM、IgG3、IgG1、IgA1、IgG2 和 IgA2 亚型，并且具有最小的体细胞突变，这表明 SARS-CoV-2 感染后会迅速发生类别转换。不同的 IGHV 链与不同的轻链配对，从而与 SARS-CoV-2 刺突蛋白的 RBD 结合。 RBD 特异性人类抗体可以通过抑制进入宿主细胞来中和 SARS-CoV-2。我们观察到，其中一种定型中和抗体可以使用 SARS-CoV-2 的临床分离株在体外抑制病毒复制。我们还发现这些 VH 克隆型存在于 10 个健康个体中的 6 个中，其中以 IgM 同种型为主。这些发现表明，刻板克隆型可以从幼稚 B 细胞中重新形成，而不是从先前暴露于类似病毒而建立的记忆 B 细胞中形成。这些克隆型的迅速和定型扩展可能发生在感染 SARS-CoV-2 的患者中，因为它们已经存在。
Stereotypic neutralizing antibody clonotypes specific for SARS-CoV-2 receptor binding domain in patients with COVID-19 and healthy individuals. Stereotypic antibodies (Abs) are produced in healthy individuals by preexisting naïve B cells that have not undergone somatic hypermutation or class switching. Kim et al. have identified stereotypic neutralizing Abs (nAbs) against SARS-CoV-2 spike protein receptor binding domain (RBD) in healthy individuals and patients with COVID-19. They detected RBD-specific stereotypic variable heavy chain (VH) Ab clonotypes composed of Ig heavy variable 3-53 (IGHV3-53) or IGHV3-66 and Ig heavy joining 6 (IGHJ6) genes in 13 of 17 patients with COVID-19. One stereotypic nAb could inhibit in vitro replication of a clinical isolate of SARS-CoV-2. These VH clonotypes were also found in 6 of 10 healthy individuals with no evidence of exposure to SARS-CoV-2, and together, these findings provide evidence of the presence of preexisting nAbs to SARS-CoV-2. Stereotypic antibody clonotypes exist in healthy individuals and may provide protective immunity against viral infections by neutralization. We observed that 13 of 17 patients with COVID-19 had stereotypic variable heavy chain (VH) antibody clonotypes directed against the receptor binding domain (RBD) of SARS-CoV-2 spike protein. These antibody clonotypes were composed of immunoglobulin heavy variable 3-53 (IGHV3-53) or IGHV3-66 and immunoglobulin heavy joining 6 (IGHJ6) genes. These clonotypes included IgM, IgG3, IgG1, IgA1, IgG2, and IgA2 subtypes and had minimal somatic mutations, which suggested swift class switching after SARS-CoV-2 infection. The different IGHV chains were paired with diverse light chains resulting in binding to the RBD of SARS-CoV-2 spike protein. Human antibodies specific for the RBD can neutralize SARS-CoV-2 by inhibiting entry into host cells. We observed that one of these stereotypic neutralizing antibodies could inhibit viral replication in vitro using a clinical isolate of SARS-CoV-2. We also found that these VH clonotypes existed in 6 of 10 healthy individuals, with IgM isotypes predominating. These findings suggest that stereotypic clonotypes can develop de novo from naïve B cells and not from memory B cells established from prior exposure to similar viruses. The expeditious and stereotypic expansion of these clonotypes may have occurred in patients infected with SARS-CoV-2 because they were already present.
登录
查看更多内容
影响因子：
7.7
作者：
Horns, Felix;Vollmers, Christopher;Quake, Stephen R.
通讯作者：
Quake, Stephen R.
影响因子：
11.4
作者：
Lefranc, MP
通讯作者：
Lefranc, MP
影响因子：
4.4
作者：
Lee, Sukmook;Yoon, Il-Hee;Chung, Junho
通讯作者：
Chung, Junho
影响因子：
12.8
作者：
Jin, Junyeong;Park, Gunwoo;Chung, Junho
通讯作者：
Chung, Junho
影响因子：
5.5
作者：
Kong, Wen-Hua;Zhao, Rong;Liu, Man-Qing
通讯作者：
Liu, Man-Qing