NHC Key Laboratory of Biosafety, National Institute for Viral Disease Control and Prevention, China CDC, Beijing 102206, China.
CAS Key Laboratory of Molecular Virology & Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai 200031, China.
EBioMedicine. 2020 Aug;58:102890. doi: 10.1016/j.ebiom.2020.102890. Epub 2020 Jul 21.
The novel coronavirus (SARS-CoV-2) shares approximately 80% whole genome sequence identity and 66% spike (S) protein identity with that of SARS-CoV. The cross-neutralization between these viruses is currently not well-defined.
Here, by using the live SARS-CoV-2 virus infection assay as well as HIV-1 based pseudotyped-virus carrying the spike (S) gene of the SARS-CoV-2 (ppSARS-2) and SARS-CoV (ppSARS), we examined whether infections with SARS-CoV and SARS-CoV-2 can induce cross-neutralizing antibodies.
We confirmed that SARS-CoV-2 infects cells via angiotensin converting enzyme 2 (ACE2), the functional receptor for SARS-CoV, and we also found that the recombinant receptor binding domain (RBD) of the S protein of SARS-CoV effectively inhibits ppSARS-2 entry in Huh7.5 cells. However, convalescent sera from SARS-CoV and SARS-CoV-2 patients showed high neutralizing activity only against the homologous virus, with no or limited cross-neutralization activity against the other pseudotyped virus. Similar results were also observed in vaccination studies in mice.
Our study demonstrates that although both SARS-CoV and SARS-CoV-2 use ACE2 as a cellular receptor, the neutralization epitopes are not shared by these two closely-related viruses, highlighting challenges towards developing a universal vaccine against SARS-CoV related viruses.
This work was supported by the National Key Research and Development Program of China, the National Major Project for Control and Prevention of Infectious Disease in China, and the One Belt and One Road Major Project for infectious diseases.
新型冠状病毒（SARS-CoV-2）与 SARS-CoV 的全基因组序列相似度约为 80%，刺突（S）蛋白相似度约为 66%。目前，这两种病毒之间的交叉中和作用尚不清楚。
在此，我们通过使用活 SARS-CoV-2 病毒感染测定法以及携带 SARS-CoV-2（ppSARS-2）和 SARS-CoV（ppSARS）刺突（S）基因的基于 HIV-1 的假型病毒，研究了 SARS-CoV 和 SARS-CoV-2 感染是否能诱导交叉中和抗体。
我们证实了 SARS-CoV-2 通过血管紧张素转换酶 2（ACE2）感染细胞，ACE2 是 SARS-CoV 的功能受体，我们还发现 SARS-CoV 的 S 蛋白的重组受体结合域（RBD）有效地抑制了 Huh7.5 细胞中 ppSARS-2 的进入。然而，SARS-CoV 和 SARS-CoV-2 患者的恢复期血清仅对同源病毒表现出高中和活性，对其他假型病毒几乎没有或没有交叉中和活性。在小鼠疫苗接种研究中也观察到了类似的结果。
我们的研究表明，尽管 SARS-CoV 和 SARS-CoV-2 均使用 ACE2 作为细胞受体，但这两种密切相关的病毒的中和表位并不相同，这突显了开发针对 SARS-CoV 相关病毒的通用疫苗所面临的挑战。
本工作得到了国家重点研发计划、国家重大传染病防治科技重大专项和“一带一路”传染病防控重大项目的支持。
