Convergent antibody responses to SARS-CoV-2 in convalescent individuals

Convergent antibody responses to SARS-CoV-2 in convalescent individuals
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DOI:
10.1038/s41586-020-2456-9
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发表时间:
2020-06-18
期刊:
影响因子:
64.8
通讯作者:
Nussenzweig, Michel C.
Nussenzweig, Michel C.
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Robbiani, Davide F.;Gaebler, Christian;Nussenzweig, Michel C.

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在冠状病毒病-2019年(新冠肺炎)大流行期间,严重急性呼吸综合征相关冠状病毒-2(SARS-CoV-2)已导致数百万人感染,并夺走了数十万人的生命。病毒进入细胞依赖于SARS-CoV-2尖峰蛋白(S)的受体结合结构域。虽然目前还没有疫苗,但抗体很可能是保护措施的关键。然而,关于人类对SARS-CoV-2(1-5)的抗体反应知之甚少。在这里,我们报告了149名新冠肺炎康复者。症状出现后平均39天采集的血浆样本具有可变的半最大假病毒中和滴度;33%的样本滴度低于50,79%的样本低于1,000,只有1%的样本滴度高于5,000。抗体测序显示,在不同个体中表达密切相关抗体的RBD特异性记忆B细胞克隆的扩增。尽管血浆滴度很低,但针对RBD上三个不同表位的抗体中和了病毒,半最大抑制浓度(IC(50)值)低至2ngml(-1)。总而言之,从新冠肺炎康复者身上获得的大多数恢复期血浆样本都不包含高水平的中和活性。然而,在所有接受测试的个体中都发现了罕见但重复出现的具有强大抗病毒活性的RBD特异性抗体,这表明旨在诱导此类抗体的疫苗可能广泛有效。尽管罕见,但从所有测试的恢复期个体中都获得了显示出强大抗病毒活性的针对SARS-CoV-2受体结合域的抗体,这表明旨在诱导此类抗体的疫苗可能广泛有效。
During the coronavirus disease-2019 (COVID-19) pandemic, severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) has led to the infection of millions of people and has claimed hundreds of thousands of lives. The entry of the virus into cells depends on the receptor-binding domain (RBD) of the spike (S) protein of SARS-CoV-2. Although there is currently no vaccine, it is likely that antibodies will be essential for protection. However, little is known about the human antibody response to SARS-CoV-2(1-5). Here we report on 149 COVID-19-convalescent individuals. Plasma samples collected an average of 39 days after the onset of symptoms had variable half-maximal pseudovirus neutralizing titres; titres were less than 50 in 33% of samples, below 1,000 in 79% of samples and only 1% of samples had titres above 5,000. Antibody sequencing revealed the expansion of clones of RBD-specific memory B cells that expressed closely related antibodies in different individuals. Despite low plasma titres, antibodies to three distinct epitopes on the RBD neutralized the virus with half-maximal inhibitory concentrations (IC(50)values) as low as 2 ng ml(-1). In conclusion, most convalescent plasma samples obtained from individuals who recover from COVID-19 do not contain high levels of neutralizing activity. Nevertheless, rare but recurring RBD-specific antibodies with potent antiviral activity were found in all individuals tested, suggesting that a vaccine designed to elicit such antibodies could be broadly effective.Although rare, antibodies against the receptor-binding domain of SARS-CoV-2 that showed potent antiviral activity were obtained from all tested convalescent individuals, suggesting that a vaccine designed to elicit such antibodies could be broadly effective.