SARS-CoV-2 B.1.1.7 and B.1.351 variants of concern induce lethal disease in K18-hACE2 transgenic mice despite convalescent plasma therapy

Horspool, A. M.; Ye, C.; Wong, T. Y.; Russ, B. P.; Lee, K. S.; Winters, M. T.; Bevere, J. R.; Kieffer, T.; Martinez, I.; Sourimant, J.; Greninger, A. L.; Plemper, R. K.; Denvir, J.; Cyphert, H. A.; Torrelles, J. B.; Martinez-Sobrido, L.; Damron, F. H.

doi:10.1101/2021.05.05.442784

bioRxiv · 10.1101/2021.05.05.442784

SARS-CoV-2 B.1.1.7 and B.1.351 variants of concern induce lethal disease in K18-hACE2 transgenic mice despite convalescent plasma therapy

Horspool, A. M.·Ye, C.·Wong, T. Y.·Russ, B. P.·Lee, K. S.·Winters, M. T.·Bevere, J. R.·Kieffer, T.·Martinez, I.·Sourimant, J.·Greninger, A. L.·Plemper, R. K.·Denvir, J.·Cyphert, H. A.·Torrelles, J. B.·Martinez-Sobrido, L.·Damron, F. H.

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Abstract

SARS-CoV-2 variants of concern (VoCs) are impacting responses to the COVID-19 pandemic. Here we present a comparison of the SARS-CoV-2 USA-WA1/2020 (WA-1) strain with B.1.1.7 and B.1.351 VoCs and identify significant differences in viral propagation in vitro and pathogenicity in vivo using K18-hACE2 transgenic mice. Passive immunization with plasma from an early pandemic SARS-CoV-2 patient resulted in significant differences in the outcome of VoC-infected mice. WA-1-infected mice were protected by plasma, B.1.1.7-infected mice were partially protected, and B.1.351-infected mice were not protected. Serological correlates of disease were different between VoC-infected mice, with B.1.351 triggering significantly altered cytokine profiles than other strains. In this study, we defined infectivity and immune responses triggered by VoCs and observed that early 2020 SARS-CoV-2 human immune plasma was insufficient to protect against challenge with B.1.1.7 and B.1.351 in the mouse model.

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Horspool, A. M., Ye, C., Wong, T. Y., Russ, B. P., Lee, K. S., Winters, M. T., Bevere, J. R., Kieffer, T., Martinez, I., Sourimant, J., Greninger, A. L., Plemper, R. K., Denvir, J., Cyphert, H. A., Torrelles, J. B., Martinez-Sobrido, L., Damron, F. H.. 2021-05-05. SARS-CoV-2 B.1.1.7 and B.1.351 variants of concern induce lethal disease in K18-hACE2 transgenic mice despite convalescent plasma therapy. https://doi.org/10.1101/2021.05.05.442784

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