@article{5ae2c57ac0d1478fb973afae833aed0d,
title = "In vivo characterization of emerging SARS-CoV-2 variant infectivity and human antibody escape potential",
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",
author = "Brandon Lam and Kung, {Yu Jui} and John Lin and Tseng, {Ssu Hsueh} and Tsai, {Ya Chea} and Liangmei He and Gianni Castiglione and Emily Egbert and Duh, {Elia J.} and Bloch, {Evan M.} and Tobian, {Aaron A.R.} and Milstone, {Aaron M.} and Roden, {Richard B.S.} and Wu, {Tzyy Choou} and Hung, {Chien Fu}",
note = "Funding Information: The authors would like to acknowledge Christopher Carter Polston and Louise Ferrall for providing administrative assistance. In addition, we would like to thank Dr. Robert Bloch and Dr. Yinghua Zhang of the biosensor core at the University of Maryland School of Medicine for support and services while completing our surface plasmon resonance experiments. This study was supported by an NIH-supported research grant (5P50CA098252). B.L. is a recipient of an NIH-supported career development fellowship (5F31CA236051). The graphical abstract was generated using BioRender. Conception and design, B.L. R.B.S.R. T.C.W. and C.-F.H.; performance of experiments, B.L. Y.J.K. J.L. S.-H.T. Y.C.T. L.H. and G.C.; analysis and interpretation of data, B.L. Y.J.K. J.L. and C.-F.H.; writing, review, and/or revision of the manuscript, B.L. Y.J.K. J.L. E.E. E.M.B. A.A.R.T. A.M.M. E.J.D. R.B.S.R. T.C.W. and C.-F.H.; study supervision, R.B.S.R.R. T.C.W. and C.-F.H. The authors declare no competing interests. One or more of the authors of this paper self-identifies as an underrepresented ethnic minority in science. While citing references scientifically relevant for this work, we also actively worked to promote gender balance in our reference list. Funding Information: The authors would like to acknowledge Christopher Carter Polston and Louise Ferrall for providing administrative assistance. In addition, we would like to thank Dr. Robert Bloch and Dr. Yinghua Zhang of the biosensor core at the University of Maryland School of Medicine for support and services while completing our surface plasmon resonance experiments. This study was supported by an NIH -supported research grant ( 5P50CA098252 ). B.L. is a recipient of an NIH -supported career development fellowship ( 5F31CA236051 ). The graphical abstract was generated using BioRender. Publisher Copyright: {\textcopyright} 2021 The Author(s)",
year = "2021",
month = oct,
day = "19",
doi = "10.1016/j.celrep.2021.109838",
language = "English (US)",
volume = "37",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "3",
}