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

Cell Rep. 2021 Oct 19;37(3):109838. doi: 10.1016/j.celrep.2021.109838. Epub 2021 Oct 5.

Authors

Affiliations

¹ 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.
² Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
³ Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
⁴ Division of Infectious Diseases, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
⁵ 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.
⁶ 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.
⁷ 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.
⁸ 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. Electronic address: [email protected].

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.

Keywords: COVID-19; N501Y; SARS-CoV-2; immune escape; in vivo modeling; pseudovirus.

Publication types

Research Support, N.I.H., Extramural

MeSH terms

Animals
Antibodies, Neutralizing / immunology
Antibodies, Viral / immunology*
COVID-19 / immunology*
COVID-19 / therapy*
COVID-19 Serotherapy
Cell Line
Cricetinae
Genetic Variation
HEK293 Cells
Humans
Immune System
Immunization, Passive / methods
In Vitro Techniques
Mice
Mutation
Nasopharynx / virology
Protein Binding
Recombinant Proteins / metabolism
SARS-CoV-2 / genetics*
SARS-CoV-2 / immunology*
Spike Glycoprotein, Coronavirus / genetics

Substances

Antibodies, Neutralizing
Antibodies, Viral
Recombinant Proteins
Spike Glycoprotein, Coronavirus
spike protein, SARS-CoV-2

Abstract

Publication types

MeSH terms

Substances

Grants and funding