Characterization of an attenuated SARS-CoV-2 variant with a deletion at the S1/S2 junction of the spike protein

Pui Wang, Siu-Ying Lau, Shaofeng Deng, Pin Chen, Bobo Wing-Yee Mok, Anna Jinxia Zhang, Andrew Chak-Yiu Lee, Kwok-Hung Chan, Rachel Chun-Yee Tam, Haoran Xu, Runhong Zhou, Wenjun Song, Li Liu, Kelvin Kai-Wang To, Jasper Fuk-Woo Chan, Zhiwei Chen, Kwok-Yung Yuen and Honglin Chen ()
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Pui Wang: The University of Hong Kong
Siu-Ying Lau: The University of Hong Kong
Shaofeng Deng: The University of Hong Kong
Pin Chen: The University of Hong Kong
Bobo Wing-Yee Mok: The University of Hong Kong
Anna Jinxia Zhang: The University of Hong Kong
Andrew Chak-Yiu Lee: The University of Hong Kong
Kwok-Hung Chan: The University of Hong Kong
Rachel Chun-Yee Tam: The University of Hong Kong
Haoran Xu: The University of Hong Kong
Runhong Zhou: The University of Hong Kong
Wenjun Song: The University of Hong Kong
Li Liu: The University of Hong Kong
Kelvin Kai-Wang To: The University of Hong Kong
Jasper Fuk-Woo Chan: The University of Hong Kong
Zhiwei Chen: The University of Hong Kong
Kwok-Yung Yuen: The University of Hong Kong
Honglin Chen: The University of Hong Kong

Nature Communications, 2021, vol. 12, issue 1, 1-10

Abstract: Abstract 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.

Date: 2021
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DOI: 10.1038/s41467-021-23166-0

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