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SARS-CoV-2 mRNA vaccination induces functionally diverse antibodies to NTD, RBD, and S2
Cell ( IF 64.5 ) Pub Date : 2021-06-08 , DOI: 10.1016/j.cell.2021.06.005
Fatima Amanat 1 , Mahima Thapa 2 , Tinting Lei 2 , Shaza M Sayed Ahmed 2 , Daniel C Adelsberg 3 , Juan Manuel Carreño 3 , Shirin Strohmeier 3 , Aaron J Schmitz 2 , Sarah Zafar 3 , Julian Q Zhou 4 , Willemijn Rijnink 3 , Hala Alshammary 3 , Nicholas Borcherding 2 , Ana Gonzalez Reiche 5 , Komal Srivastava 3 , Emilia Mia Sordillo 6 , Harm van Bakel 7 , , Jackson S Turner 2 , Goran Bajic 3 , Viviana Simon 8 , Ali H Ellebedy 9 , Florian Krammer 3
Affiliation  

In this study we profiled vaccine-induced polyclonal antibodies as well as plasmablast-derived mAbs from individuals who received SARS-CoV-2 spike mRNA vaccine. Polyclonal antibody responses in vaccinees were robust and comparable to or exceeded those seen after natural infection. However, the ratio of binding to neutralizing antibodies after vaccination was greater than that after natural infection and, at the monoclonal level, we found that the majority of vaccine-induced antibodies did not have neutralizing activity. We also found a co-dominance of mAbs targeting the NTD and RBD of SARS-CoV-2 spike and an original antigenic-sin like backboost to spikes of seasonal human coronaviruses OC43 and HKU1. Neutralizing activity of NTD mAbs but not RBD mAbs against a clinical viral isolate carrying E484K as well as extensive changes in the NTD was abolished, suggesting that a proportion of vaccine-induced RBD binding antibodies may provide substantial protection against viral variants carrying single E484K RBD mutations.



中文翻译:

SARS-CoV-2 mRNA 疫苗接种可诱导针对 NTD、RBD 和 S2 的功能多样的抗体

在这项研究中,我们分析了疫苗诱导的多克隆抗体以及来自接受 SARS-CoV-2 刺突 mRNA 疫苗的个体的浆母细胞衍生的单克隆抗体。疫苗接种者的多克隆抗体反应非常强劲,与自然感染后的反应相当或超过。然而,接种疫苗后与中和抗体结合的比例高于自然感染后的比例,并且在单克隆水平上,我们发现大多数疫苗诱导的抗体不具有中和活性。我们还发现,针对 SARS-CoV-2 刺突的 NTD 和 RBD 的单克隆抗体与针对季节性人类冠状病毒 OC43 和 HKU1 刺突的原始抗原罪状反向增强具有共同优势。NTD mAb(而非 RBD mAb)对携带 E484K 的临床病毒分离株的中和活性以及 NTD 的广泛变化被取消,这表明一定比例的疫苗诱导的 RBD 结合抗体可能对携带单一 E484K RBD 突变的病毒变体提供实质性保护。

更新日期:2021-07-22
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