Department of Microbiology and State Key Laboratory for Emerging Infectious Diseases, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, SAR, China.
State Key Laboratory of Respiratory Disease, Institute of Integration of Traditional and Western Medicine, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, China.
Nat Commun. 2021 May 13;12(1):2790. doi: 10.1038/s41467-021-23166-0.
SARS-CoV-2 is of zoonotic origin and contains a PRRA polybasic cleavage motif which is considered critical for efficient infection and transmission in humans. We previously reported on a panel of attenuated SARS-CoV-2 variants with deletions at the S1/S2 junction of the spike protein. Here, we characterize pathogenicity, immunogenicity, and protective ability of a further cell-adapted SARS-CoV-2 variant, Ca-DelMut, in in vitro and in vivo systems. Ca-DelMut replicates more efficiently than wild type or parental virus in Vero E6 cells, but causes no apparent disease in hamsters, despite replicating in respiratory tissues. Unlike wild type virus, Ca-DelMut causes no obvious pathological changes and does not induce elevation of proinflammatory cytokines, but still triggers a strong neutralizing antibody and T cell response in hamsters and mice. Ca-DelMut immunized hamsters challenged with wild type SARS-CoV-2 are fully protected, with little sign of virus replication in the upper or lower respiratory tract, demonstrating sterilizing immunity.
SARS-CoV-2 是一种人畜共患病原体，其刺突蛋白 S1/S2 连接处存在一个 PRRA 多碱性切割基序，被认为对人类的高效感染和传播至关重要。我们之前曾报道过一组在 S1/S2 连接处缺失的减毒 SARS-CoV-2 变体。在此，我们在体外和体内系统中对进一步细胞适应的 SARS-CoV-2 变体 Ca-DelMut 的致病性、免疫原性和保护能力进行了表征。Ca-DelMut 在 Vero E6 细胞中的复制效率高于野生型或亲本病毒，但在仓鼠中不会引起明显疾病，尽管在呼吸道组织中复制。与野生型病毒不同，Ca-DelMut 不会引起明显的病理变化，也不会诱导促炎细胞因子的升高，但仍能在仓鼠和小鼠中引发强烈的中和抗体和 T 细胞反应。用野生型 SARS-CoV-2 攻毒的 Ca-DelMut 免疫仓鼠得到完全保护，在上呼吸道或下呼吸道几乎没有病毒复制的迹象，证明具有杀菌性免疫力。
