Role of Immunoglobulin M and A Antibodies in the Neutralization of Severe Acute Respiratory Syndrome Coronavirus 2.
Role of Immunoglobulin M and A Antibodies in the Neutralization of Severe Acute Respiratory Syndrome Coronavirus 2.
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DOI：
10.1093/infdis/jiaa784
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发表时间：
2021-03-29
期刊：
影响因子：
--
通讯作者：
Hioe CE
中科院分区：
文献类型：
--
作者：
Klingler J;Weiss S;Itri V;Liu X;Oguntuyo KY;Stevens C;Ikegame S;Hung CT;Enyindah-Asonye G;Amanat F;Baine I;Arinsburg S;Bandres JC;Kojic EM;Stoever J;Jurczyszak D;Bermudez-Gonzalez M;Nádas A;Liu S;Lee B;Zolla-Pazner S;Hioe CE
严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 已感染全球数百万人。病毒感染需要刺突蛋白的受体结合域（RBD）。尽管研究表明抗尖峰抗体和 RBD 抗体在动物模型中具有保护作用，并且恢复期血浆是一种有前途的治疗选择，但人们对能够阻断感染的免疫球蛋白同种型知之甚少。我们使用多重微珠测定法研究了恢复期和急性期血浆/血清样本中的尖峰和 RBD 特异性免疫球蛋白同种型。我们还使用水泡性口炎假病毒测定法测定了血浆和血清样品以及纯化的免疫球蛋白组分中的病毒中和活性。所有或几乎所有受试者都会产生不同水平的 Spike 和 RBD 特异性免疫球蛋白 (Ig) M、IgG1 和 IgA1，并在感染后早期检测到。所有样品均显示出中和活性。回归分析显示，IgM 和 IgG1 对中和作用贡献最大，与 IgM 和 IgG 组分的中和效力一致。 IgA 也表现出中和活性，但效力较低。 IgG、IgM 和 IgA 是用于治疗 2019 年冠状病毒病 (COVID-19) 的恢复期血浆的关键成分。 2019 年冠状病毒病 (COVID-19) 恢复期患者的血浆中存在针对严重急性呼吸综合征冠状病毒 2 刺突糖蛋白及其受体结合域的免疫球蛋白 (Ig) M、IgG1 和 IgA1 抗体。 IgG、IgM 和 IgA 有助于中和病毒，为最佳选择用于 COVID-19 治疗的恢复期血浆提供基础。
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected millions of people globally. Virus infection requires the receptor-binding domain (RBD) of the spike protein. Although studies have demonstrated anti-spike and -RBD antibodies to be protective in animal models, and convalescent plasma as a promising therapeutic option, little is known about immunoglobulin isotypes capable of blocking infection. We studied spike- and RBD-specific immunoglobulin isotypes in convalescent and acute plasma/serum samples using a multiplex bead assay. We also determined virus neutralization activities in plasma and serum samples, and purified immunoglobulin fractions using a vesicular stomatitis pseudovirus assay. Spike- and RBD-specific immunoglobulin (Ig) M, IgG1, and IgA1 were produced by all or nearly all subjects at variable levels and detected early after infection. All samples displayed neutralizing activity. Regression analyses revealed that IgM and IgG1 contributed most to neutralization, consistent with IgM and IgG fractions’ neutralization potency. IgA also exhibited neutralizing activity, but with lower potency. IgG, IgM, and IgA are critical components of convalescent plasma used for treatment of coronavirus disease 2019 (COVID-19). Immunoglobulin (Ig) M, IgG1, and IgA1 antibodies against severe acute respiratory syndrome coronavirus 2 spike glycoprotein and its receptor-binding domain are present in plasma from patients with convalescent coronavirus disease 2019 (COVID-19). IgG, IgM, and IgA contribute to virus neutralization, providing the basis for optimal selection of convalescent plasma for COVID-19 treatment.
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