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
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.
