Pathogenicity, immunogenicity, and protective ability of an attenuated SARS-CoV-2 variant with a deletion at the S1/S2 junction of the spike protein

Wang, P.; Lau, S.-Y.; Deng, S.; Chen, P.; Mok, B. W.-Y.; Zhang, A. J.; Lee, A. C.-Y.; Chan, K.-H.; Song, W.; To, K. K.-W.; Chen, J. F.-W.; Yuen, K.-Y.; Chen, H.

doi:10.1101/2020.08.24.264192

bioRxiv · 10.1101/2020.08.24.264192

Pathogenicity, immunogenicity, and protective ability of an attenuated SARS-CoV-2 variant with a deletion at the S1/S2 junction of the spike protein

Wang, P.·Lau, S.-Y.·Deng, S.·Chen, P.·Mok, B. W.-Y.·Zhang, A. J.·Lee, A. C.-Y.·Chan, K.-H.·Song, W.·To, K. K.-W.·Chen, J. F.-W.·Yuen, K.-Y.·Chen, H.

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Abstract

SARS-CoV-2 contains a PRRA polybasic cleavage motif considered critical for efficient infection and transmission in humans. We previously reported that virus variants with spike protein S1/S2 junction deletions spanning this motif are attenuated. Here we characterize a further cell-adapted SARS-CoV-2 variant, Ca-DelMut. Ca-DelMut replicates more efficiently than wild type or parental virus in cells, but causes no apparent disease in hamsters, despite replicating in respiratory tissues. Unlike wild type virus, Ca-DelMut does not induce proinflammatory cytokines in hamster infections, but still triggers a strong neutralizing antibody response. Ca-DelMut-immunized hamsters challenged with wild type SARS-CoV-2 are fully protected, demonstrating sterilizing immunity.

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Wang, P., Lau, S.-Y., Deng, S., Chen, P., Mok, B. W.-Y., Zhang, A. J., Lee, A. C.-Y., Chan, K.-H., Song, W., To, K. K.-W., Chen, J. F.-W., Yuen, K.-Y., Chen, H.. 2020-08-24. Pathogenicity, immunogenicity, and protective ability of an attenuated SARS-CoV-2 variant with a deletion at the S1/S2 junction of the spike protein. https://doi.org/10.1101/2020.08.24.264192

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