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

Cell Reports (Oct 2021)

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

Affiliations

Brandon Lam: Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Graduate Program in Immunology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Yu Jui Kung: Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
John Lin: Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Ssu-Hsueh Tseng: Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Ya Chea Tsai: Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Liangmei He: Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Gianni Castiglione: Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Emily Egbert: Division of Infectious Diseases, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Elia J. Duh: Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Evan M. Bloch: Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Aaron A.R. Tobian: Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Aaron M. Milstone: Division of Infectious Diseases, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA; Department of Hospital Epidemiology and Infection Control, The Johns Hopkins Hospital, Baltimore, MD 21205, USA
Richard B.S. Roden: Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Obstetrics and Gynecology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Tzyy-Choou Wu: Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Obstetrics and Gynecology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Molecular Microbiology and Immunology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Chien-Fu Hung: Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Corresponding author

Journal volume & issue: Vol. 37, no. 3
p. 109838

Abstract

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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.

Published in Cell Reports

ISSN: 2211-1247 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General)
Website: http://www.cell.com/cell-reports/home

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