三名新冠肺炎患者针对严重急性呼吸综合征冠状病毒2(SARS-CoV-2)结构蛋白的纵向抗体动态显示IgA、IgM和IgG同时产生。

Longitudinal Antibody Dynamics Against Structural Proteins of SARS-CoV-2 in Three COVID-19 Patients Shows Concurrent Development of IgA, IgM, and IgG.

作者信息

Jamiruddin Mohd Raeed, Haq Md Ahsanul, Tomizawa Kazuhito, Kobatake Eiry, Mie Masayasu, Ahmed Sohel, Khandker Shahad Saif, Ali Tamanna, Jahan Nowshin, Oishee Mumtarin Jannat, Khondoker Mohib Ullah, Sil Bijon Kumar, Haque Mainul, Adnan Nihad

机构信息

Department of Pharmacy, BRAC University, Dhaka, 1212, Bangladesh.

Gonoshasthaya-RNA Molecular Diagnostic & Research Center, Dhaka, 1205, Bangladesh.

出版信息

J Inflamm Res. 2021 Jun 14;14:2497-2506. doi: 10.2147/JIR.S313188. eCollection 2021.

Abstract

BACKGROUND

Dynamics and persistence of neutralizing and non-neutralizing antibodies can give us the knowledge required for serodiagnosis, disease management, and successful vaccine design and development. The disappearance of antibodies, absence of humoral immunity activation, and sporadic reinfection cases emphasize the importance of longitudinal antibody dynamics against variable structural antigens.

METHODS

In this study, twenty-five healthy subjects working in a SARS-COV-2 serodiagnostic assay development project were enrolled, and their sign and symptoms were followed up to six months. Three subjects showed COVID-19-like symptoms, and three subjects' antibody dynamics were followed over 120 days by analyzing 516 samples. We have developed 12 different types of in-house ELISAs to observe the kinetics of IgG, IgM, and IgA against four SARS-CoV-2 proteins, namely nucleocapsid, RBD, S1, and whole spike (S1+S2). For the development of these assays, 30-104 pre-pandemic samples were taken as negative controls and 83 RT-qPCR positive samples as positive ones.

RESULTS

All three subjects presented COVID-19-like symptoms twice, with mild symptoms in the first episode were severe in the second, and RT-qPCR confirmed the latter. The initial episode did not culminate with any significant antibody development, while a multifold increase in IgG antibodies characterized the second episode. Interestingly, IgG antibody development concurrent with IgM and IgA and persisted, whereas the latter two weans off rather quickly if appeared.

CONCLUSION

Antibody kinetics observed in this study can provide a pathway to the successful development of sero-diagnostics and epidemiologists to predict the fate of vaccination currently in place.

摘要

背景

中和抗体和非中和抗体的动态变化及持久性可为我们提供血清学诊断、疾病管理以及成功设计和开发疫苗所需的知识。抗体的消失、体液免疫激活的缺失以及散发性再感染病例强调了针对可变结构抗原的纵向抗体动态变化的重要性。

方法

在本研究中,招募了25名参与SARS-CoV-2血清学诊断检测开发项目的健康受试者,并对他们的体征和症状进行了长达6个月的随访。3名受试者出现了类似COVID-19的症状,通过分析516份样本对3名受试者的抗体动态变化进行了120天的跟踪。我们开发了12种不同类型的内部酶联免疫吸附测定法(ELISA),以观察针对四种SARS-CoV-2蛋白(即核衣壳蛋白、受体结合域、S1亚基和全长刺突蛋白(S1+S2))的IgG、IgM和IgA的动力学变化。为了开发这些检测方法,将30-104份疫情前的样本作为阴性对照,83份逆转录定量聚合酶链反应(RT-qPCR)阳性样本作为阳性对照。

结果

所有3名受试者均出现了两次类似COVID-19的症状,第一次发作时症状较轻,第二次发作时症状较重,RT-qPCR证实了第二次发作。第一次发作时并未出现任何显著的抗体产生,而第二次发作时IgG抗体呈数倍增加。有趣的是,IgG抗体与IgM和IgA同时产生并持续存在,而后两者如果出现则很快消失。

结论

本研究中观察到的抗体动力学可为血清学诊断的成功开发提供途径,并帮助流行病学家预测当前疫苗接种的效果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d16/8214341/9200aa0d92e6/JIR-14-2497-g0001.jpg

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