Steenhuis Maurice, van Mierlo Gerard, Derksen Ninotska Il, Ooijevaar-de Heer Pleuni, Kruithof Simone, Loeff Floris L, Berkhout Lea C, Linty Federica, Reusken Chantal, Reimerink Johan, Hogema Boris, Zaaijer Hans, van de Watering Leo, Swaneveld Francis, van Gils Marit J, Bosch Berend Jan, van Ham S Marieke, Ten Brinke Anja, Vidarsson Gestur, van der Schoot Ellen C, Rispens Theo
Department of Immunopathology Sanquin Research Amsterdam The Netherlands.
Landsteiner Laboratory Amsterdam University Medical Centre University of Amsterdam Amsterdam The Netherlands.
Clin Transl Immunology. 2021 May 16;10(5):e1285. doi: 10.1002/cti2.1285. eCollection 2021.
Characterisation of the human antibody response to SARS-CoV-2 infection is vital for serosurveillance purposes and for treatment options such as transfusion with convalescent plasma or immunoglobulin products derived from convalescent plasma. In this study, we longitudinally and quantitatively analysed antibody responses in RT-PCR-positive SARS-CoV-2 convalescent adults during the first 250 days after onset of symptoms.
We measured antibody responses to the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein and the nucleocapsid protein in 844 longitudinal samples from 151 RT-PCR-positive SARS-CoV-2 convalescent adults. With a median of 5 (range 2-18) samples per individual, this allowed quantitative analysis of individual longitudinal antibody profiles. Kinetic profiles were analysed by mixed-effects modelling.
All donors were seropositive at the first sampling moment, and only one donor seroreverted during follow-up analysis. Anti-RBD IgG and anti-nucleocapsid IgG levels declined with median half-lives of 62 and 59 days, respectively, 2-5 months after symptom onset, and several-fold variation in half-lives of individuals was observed. The rate of decline of antibody levels diminished during extended follow-up, which points towards long-term immunological memory. The magnitude of the anti-RBD IgG response correlated well with neutralisation capacity measured in a classic plaque reduction assay and in an in-house developed competitive assay.
The result of this study gives valuable insight into the long-term longitudinal response of antibodies to SARS-CoV-2.
了解人类对严重急性呼吸综合征冠状病毒2(SARS-CoV-2)感染的抗体反应,对于血清学监测以及诸如输注康复期血浆或源自康复期血浆的免疫球蛋白产品等治疗选择至关重要。在本研究中,我们对症状出现后的前250天内,逆转录聚合酶链反应(RT-PCR)检测呈阳性的SARS-CoV-2康复期成年患者的抗体反应进行了纵向定量分析。
我们检测了151例RT-PCR检测呈阳性的SARS-CoV-2康复期成年患者的844份纵向样本中针对SARS-CoV-2刺突蛋白受体结合域(RBD)和核衣壳蛋白的抗体反应。每位个体的样本中位数为5份(范围为2至18份),这使得能够对个体纵向抗体谱进行定量分析。通过混合效应模型分析动力学曲线。
所有供体在首次采样时血清学检测均为阳性,且在后续分析中只有一名供体血清学检测结果转阴。症状出现后2至5个月,抗RBD IgG和抗核衣壳IgG水平下降,半衰期中位数分别为62天和59天,并且观察到个体半衰期存在数倍差异。在延长随访期间,抗体水平下降速率降低,这表明存在长期免疫记忆。抗RBD IgG反应的强度与经典蚀斑减少试验和内部开发的竞争试验中测得的中和能力密切相关。
本研究结果为抗体对SARS-CoV-2的长期纵向反应提供了有价值的见解。