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Persistence and decay of human antibody responses to the receptor binding domain of SARS-CoV-2 spike protein in COVID-19 patients
Science Immunology ( IF 17.6 ) Pub Date : 2020-10-08 , DOI: 10.1126/sciimmunol.abe0367
Anita S Iyer 1, 2 , Forrest K Jones 3 , Ariana Nodoushani 1 , Meagan Kelly 1 , Margaret Becker 1 , Damien Slater 1 , Rachel Mills 1 , Erica Teng 1 , Mohammad Kamruzzaman 1 , Wilfredo F Garcia-Beltran 4 , Michael Astudillo 4 , Diane Yang 4 , Tyler E Miller 4 , Elizabeth Oliver 1 , Stephanie Fischinger 5 , Caroline Atyeo 5 , A John Iafrate 4 , Stephen B Calderwood 1, 2, 6 , Stephen A Lauer 3 , Jingyou Yu 7 , Zhenfeng Li 7 , Jared Feldman 5 , Blake M Hauser 5 , Timothy M Caradonna 5 , John A Branda 4 , Sarah E Turbett 1, 2, 4 , Regina C LaRocque 1, 2 , Guillaume Mellon 1 , Dan H Barouch 5, 7 , Aaron G Schmidt 5, 6 , Andrew S Azman 3 , Galit Alter 5 , Edward T Ryan 1, 2, 8 , Jason B Harris 1, 9 , Richelle C Charles 1, 2
Affiliation  

We measured plasma and/or serum antibody responses to the receptor-binding domain (RBD) of the spike (S) protein of SARS-CoV-2 in 343 North American patients infected with SARS-CoV-2 (of which 93% required hospitalization) up to 122 days after symptom onset and compared them to responses in 1548 individuals whose blood samples were obtained prior to the pandemic. After setting seropositivity thresholds for perfect specificity (100%), we estimated sensitivities of 95% for IgG, 90% for IgA, and 81% for IgM for detecting infected individuals between 15 and 28 days after symptom onset. While the median time to seroconversion was nearly 12 days across all three isotypes tested, IgA and IgM antibodies against RBD were short-lived with median times to seroreversion of 71 and 49 days after symptom onset. In contrast, anti-RBD IgG responses decayed slowly through 90 days with only 3 seropositive individuals seroreverting within this time period. IgG antibodies to SARS-CoV-2 RBD were strongly correlated with anti-S neutralizing antibody titers, which demonstrated little to no decrease over 75 days since symptom onset. We observed no cross-reactivity of the SARS-CoV-2 RBD-targeted antibodies with other widely circulating coronaviruses (HKU1, 229 E, OC43, NL63). These data suggest that RBD-targeted antibodies are excellent markers of previous and recent infection, that differential isotype measurements can help distinguish between recent and older infections, and that IgG responses persist over the first few months after infection and are highly correlated with neutralizing antibodies.



中文翻译:


COVID-19 患者中人类抗体对 SARS-CoV-2 刺突蛋白受体结合域的反应的持续性和衰减



我们测量了 343 名感染 SARS-CoV-2 的北美患者(其中 93% 需要住院治疗)的血浆和/或血清抗体对 SARS-CoV-2 刺突 (S) 蛋白受体结合域 (RBD) 的反应)在症状出现后长达 122 天,并将其与大流行前获取血液样本的 1548 名个体的反应进行比较。在设定完美特异性的血清阳性阈值 (100%) 后,我们估计在症状出现后 15 至 28 天之间检测感染个体的 IgG 灵敏度为 95%,IgA 为 90%,IgM 为 81%。虽然所有测试的三种同种型的血清转换中位时间接近 12 天,但针对 RBD 的 IgA 和 IgM 抗体的寿命很短,症状出现后血清转换的中位时间分别为 71 天和 49 天。相比之下,抗 RBD IgG 反应在 90 天内缓慢衰减,只有 3 名血清阳性个体在这段时间内出现血清逆转。 SARS-CoV-2 RBD 的 IgG 抗体与抗 S 中和抗体滴度密切相关,在症状出现后 75 天内,该抗体滴度几乎没有下降或没有下降。我们观察到 SARS-CoV-2 RBD 靶向抗体与其他广泛传播的冠状病毒(HKU1、229 E、OC43、NL63)没有交叉反应。这些数据表明,RBD 靶向抗体是先前和最近感染的极好标志物,差异同种型测量可以帮助区分最近和较早的感染,并且 IgG 反应在感染后的最初几个月持续存在,并且与中和抗体高度相关。

更新日期:2020-10-08
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