SARS-CoV-2 B.1.1.7 (alpha) and B.1.351 (beta) variants induce pathogenic patterns in K18-hACE2 transgenic mice distinct from early strains

Peter Radvak, Hyung-Joon Kwon, Martina Kosikova, Uriel Ortega-Rodriguez, Ruoxuan Xiang, Je-Nie Phue, Rong-Fong Shen, James Rozzelle, Neeraj Kapoor, Taylor Rabara, Jeff Fairman and Hang Xie ()
Additional contact information
Peter Radvak: United States Food and Drug Administration
Hyung-Joon Kwon: United States Food and Drug Administration
Martina Kosikova: United States Food and Drug Administration
Uriel Ortega-Rodriguez: United States Food and Drug Administration
Ruoxuan Xiang: United States Food and Drug Administration
Je-Nie Phue: United States Food and Drug Administration
Rong-Fong Shen: United States Food and Drug Administration
James Rozzelle: Vaxcyte, Inc
Neeraj Kapoor: Vaxcyte, Inc
Taylor Rabara: Vaxcyte, Inc
Jeff Fairman: Vaxcyte, Inc
Hang Xie: United States Food and Drug Administration

Nature Communications, 2021, vol. 12, issue 1, 1-15

Abstract: Abstract SARS-CoV-2 variants of concern (VOC) B.1.1.7 (alpha) and B.1.351 (beta) show increased transmissibility and enhanced antibody neutralization resistance. Here we demonstrate in K18-hACE2 transgenic mice that B.1.1.7 and B.1.351 are 100-fold more lethal than the original SARS-CoV-2 bearing 614D. B.1.1.7 and B.1.351 cause more severe organ lesions in K18-hACE2 mice than early SARS-CoV-2 strains bearing 614D or 614G, with B.1.1.7 and B.1.351 infection resulting in distinct tissue-specific cytokine signatures, significant D-dimer depositions in vital organs and less pulmonary hypoxia signaling before death. However, K18-hACE2 mice with prior infection of early SARS-CoV-2 strains or intramuscular immunization of viral spike or receptor binding domain are resistant to the lethal reinfection of B.1.1.7 or B.1.351, despite having reduced neutralization titers against these VOC than early strains. Our results thus distinguish pathogenic patterns in K18-hACE2 mice caused by B.1.1.7 and B.1.351 infection from those induced by early SARS-CoV-2 strains, and help inform potential medical interventions for combating COVID-19.

Date: 2021
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DOI: 10.1038/s41467-021-26803-w

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