1. In vivo characterization of emerging SARS-CoV-2 variant infectivity and human antibody escape potential
- Author
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Evan M. Bloch, Yu Jui Kung, John H. Lin, Tzyy Choou Wu, Liangmei He, Ya Chea Tsai, Ssu-Hsueh Tseng, Chien Fu Hung, Brandon Lam, Elia J. Duh, Gianni M Castiglione, Aaron M. Milstone, Aaron A.R. Tobian, Richard B. S. Roden, and Emily R Egbert
- Subjects
QH301-705.5 ,Virulence ,Plasma protein binding ,In Vitro Techniques ,Antibodies, Viral ,General Biochemistry, Genetics and Molecular Biology ,Neutralization ,Article ,Cell Line ,Mice ,Immune system ,In vivo ,Cricetinae ,Nasopharynx ,Animals ,Humans ,N501Y ,Biology (General) ,COVID-19 Serotherapy ,Infectivity ,pseudovirus ,biology ,SARS-CoV-2 ,Immunization, Passive ,in vivo modeling ,immune escape ,Respiratory infection ,Genetic Variation ,COVID-19 ,Virology ,Antibodies, Neutralizing ,Recombinant Proteins ,HEK293 Cells ,Immune System ,Mutation ,Spike Glycoprotein, Coronavirus ,biology.protein ,Antibody ,Protein Binding - 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., Graphical abstract, Lam et al. develop a model of SARS-CoV-2 infection in laboratory mice. This allows researchers to study the threat of emerging variants in a more physiological context than by using cell culture systems. Interactions between SARS-CoV-2 variants and immunity are explored in the airway of mice.
- Published
- 2021