Cell Reports
Volume 37, Issue 3, 19 October 2021, 109838
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Article
In vivo characterization of emerging SARS-CoV-2 variant infectivity and human antibody escape potential

https://doi.org/10.1016/j.celrep.2021.109838Get rights and content
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Highlights

  • N501Y RBD SARS-CoV-2 PsVs achieve high-level infection in murine respiratory tract

  • South Africa and India variant PsVs attain the most robust airway infection in mice

  • SARS-CoV-2 variants carrying E484 perturbations exhibit immune escape in vivo

  • High-titer COVID-19+ or vaccinated individuals control emerging variants the strongest

Summary

As severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spreads, variants with enhanced virulence and transmissibility have emerged. Although in vitro systems allow rapid characterization, they do not fully recapitulate the dynamic interaction of virions and neutralizing antibodies in the airway. Here, we demonstrate that the N501Y variant permits respiratory infection in unmodified mice. We utilize N501Y to survey in vivo pseudovirus infection dynamics and susceptibility to reinfection with the L452R (Los Angeles), K417N + E484K (South Africa), and L452R + K417N + E484Q (India) variants. Human coronavirus disease 2019 (COVID-19)+ or vaccinated antibody isotypes, titers, variant receptor binding domain (RBD) binding, and neutralization potential are studied, revealing numerous significant correlations. Immune escape of the K417N + E484K variant is observed because infection can be appreciated in the nasopharynx, but not lungs, of mice transferred with low-antibody-tier plasma. Conversely, near-complete protection is observed in animals receiving high-antibody-tier plasma, a phenomenon that can only be appreciated in vivo.

Keywords

SARS-CoV-2
COVID-19
pseudovirus
in vivo modeling
N501Y
immune escape

Data and code availability

  • All data reported in this paper will be shared by the lead contact upon request.

  • This paper does not report original code.

  • Any additional information required to reanalyze the data reported in this paper is available from the lead contact upon request.

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