Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Cell. 2021 Jul 22;184(15):3936-3948.e10. doi: 10.1016/j.cell.2021.06.005. Epub 2021 Jun 8.
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.
在这项研究中，我们对接受 SARS-CoV-2 刺突 mRNA 疫苗的个体的疫苗诱导的多克隆抗体以及浆母细胞衍生的 mAb 进行了分析。疫苗接种者的多克隆抗体反应强烈，与自然感染后相比相当或更高。然而，接种后与中和抗体结合的比例高于自然感染后，并且在单克隆水平上，我们发现大多数疫苗诱导的抗体没有中和活性。我们还发现针对 SARS-CoV-2 刺突的 NTD 和 RBD 的 mAb 共同主导，并且对季节性人类冠状病毒 OC43 和 HKU1 的刺突具有原始抗原性相似的后助推作用。对携带 E484K 的临床病毒分离株的 NTD mAb 的中和活性以及 NTD 的广泛变化被消除，这表明一部分疫苗诱导的 RBD 结合抗体可能对携带单个 E484K RBD 突变的病毒变体提供实质性保护。
