In vivo characterization of emerging SARS-CoV-2 variant infectivity and human antibody escape potential

Brandon Lam; Yu Jui Kung; John Lin; Ssu Hsueh Tseng; Ya Chea Tsai; Liangmei He; Gianni Castiglione; Emily Egbert; Elia J. Duh; Evan M. Bloch; Aaron A.R. Tobian; Aaron M. Milstone; Richard B.S. Roden; Tzyy Choou Wu; Chien Fu Hung

doi:10.1016/j.celrep.2021.109838

In vivo characterization of emerging SARS-CoV-2 variant infectivity and human antibody escape potential

Brandon Lam, Yu Jui Kung, John Lin, Ssu Hsueh Tseng, Ya Chea Tsai, Liangmei He, Gianni Castiglione, Emily Egbert, Elia J. Duh, Evan M. Bloch, Aaron A.R. Tobian, Aaron M. Milstone, Richard B.S. Roden, Tzyy Choou Wu, Chien Fu Hung

School of Medicine

Research output: Contribution to journal › Article › peer-review

Abstract

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.

Original language	English (US)
Article number	109838
Journal	Cell Reports
Volume	37
Issue number	3
DOIs	https://doi.org/10.1016/j.celrep.2021.109838
State	Published - Oct 19 2021

Keywords

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

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

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10.1016/j.celrep.2021.109838

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Lam, B., Kung, Y. J., Lin, J., Tseng, S. H., Tsai, Y. C., He, L., Castiglione, G., Egbert, E., Duh, E. J., Bloch, E. M., Tobian, A. A. R., Milstone, A. M., Roden, R. B. S., Wu, T. C., & Hung, C. F. (2021). In vivo characterization of emerging SARS-CoV-2 variant infectivity and human antibody escape potential. Cell Reports, 37(3), Article 109838. https://doi.org/10.1016/j.celrep.2021.109838

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abstract = "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.",

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AU - Tsai, Ya Chea

AU - He, Liangmei

AU - Castiglione, Gianni

AU - Egbert, Emily

AU - Duh, Elia J.

AU - Bloch, Evan M.

AU - Tobian, Aaron A.R.

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In vivo characterization of emerging SARS-CoV-2 variant infectivity and human antibody escape potential

Abstract

Keywords

ASJC Scopus subject areas

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