Laboratory of Aging Research and Cancer Drug Target, State Key Laboratory of Biotherapy and Cancer Center, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, China.
National Kunming High-level Biosafety Primate Research Center, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Yunnan, China.
Nature. 2020 Oct;586(7830):572-577. doi: 10.1038/s41586-020-2599-8. Epub 2020 Jul 29.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes a respiratory disease called coronavirus disease 2019 (COVID-19), the spread of which has led to a pandemic. An effective preventive vaccine against this virus is urgently needed. As an essential step during infection, SARS-CoV-2 uses the receptor-binding domain (RBD) of the spike protein to engage with the receptor angiotensin-converting enzyme 2 (ACE2) on host cells. Here we show that a recombinant vaccine that comprises residues 319-545 of the RBD of the spike protein induces a potent functional antibody response in immunized mice, rabbits and non-human primates (Macaca mulatta) as early as 7 or 14 days after the injection of a single vaccine dose. The sera from the immunized animals blocked the binding of the RBD to ACE2, which is expressed on the cell surface, and neutralized infection with a SARS-CoV-2 pseudovirus and live SARS-CoV-2 in vitro. Notably, vaccination also provided protection in non-human primates to an in vivo challenge with SARS-CoV-2. We found increased levels of RBD-specific antibodies in the sera of patients with COVID-19. We show that several immune pathways and CD4 T lymphocytes are involved in the induction of the vaccine antibody response. Our findings highlight the importance of the RBD domain in the design of SARS-CoV-2 vaccines and provide a rationale for the development of a protective vaccine through the induction of antibodies against the RBD domain.
严重急性呼吸系统综合征冠状病毒 2（SARS-CoV-2）引起一种称为 2019 年冠状病毒病（COVID-19）的呼吸道疾病，其传播导致了大流行。迫切需要针对这种病毒的有效预防疫苗。作为感染过程中的一个重要步骤，SARS-CoV-2 使用 Spike 蛋白的受体结合结构域（RBD）与宿主细胞上的血管紧张素转换酶 2（ACE2）受体结合。在这里，我们展示了一种由 Spike 蛋白的 RBD 的残基 319-545 组成的重组疫苗，在免疫接种小鼠、兔子和非人类灵长类动物（猕猴）后 7 或 14 天内，就可引发强烈的功能性抗体反应。免疫动物的血清可阻断 RBD 与 ACE2 的结合，ACE2 表达在细胞表面，并中和体外 SARS-CoV-2 假病毒和活 SARS-CoV-2 的感染。值得注意的是，疫苗接种还为非人类灵长类动物提供了对 SARS-CoV-2 体内攻击的保护。我们发现 COVID-19 患者血清中的 RBD 特异性抗体水平升高。我们表明，几种免疫途径和 CD4 T 淋巴细胞参与了疫苗抗体反应的诱导。我们的研究结果强调了 RBD 结构域在 SARS-CoV-2 疫苗设计中的重要性，并为通过诱导针对 RBD 结构域的抗体来开发保护疫苗提供了依据。
