@article{a2f3fddaeaeb48649d43def2e9404318,
title = "High Potency of a Bivalent Human VH Domain in SARS-CoV-2 Animal Models",
abstract = "A high-affinity human antibody domain, VH ab8, specific for SARS-CoV-2, bound to all three S protomers competing with ACE2. The relatively small size and bivalency of VH-Fc ab8 contributed to its high potency in two animal models of infection.",
keywords = "SARS-CoV-2, electron microscopy, human V antibody domain, mouse and hamster models, virus neutralization",
author = "Wei Li and Alexandra Sch{\"a}fer and Kulkarni, {Swarali S.} and Xianglei Liu and Martinez, {David R.} and Chuan Chen and Zehua Sun and Leist, {Sarah R.} and Aleksandra Drelich and Liyong Zhang and Ura, {Marcin L.} and Alison Berezuk and Sagar Chittori and Karoline Leopold and Dhiraj Mannar and Srivastava, {Shanti S.} and Xing Zhu and Peterson, {Eric C.} and Tseng, {Chien Te} and Mellors, {John W.} and Darryl Falzarano and Sriram Subramaniam and Baric, {Ralph S.} and Dimitrov, {Dimiter S.}",
note = "Funding Information: We would like to thank the members of our group, Dontcho Jelev, Megan Shi, Cynthia Adams, Du-San Baek, Ye-Jin Kim, and Xiaojie Chu for their helpful discussions. We thank Dr. Kevin McCormick from the University of Pittsburgh, Rui Gong from the Institute of Virology in Wuhan, and Rachel Fong from Integral Molecular for helpful suggestions. We would also like to thank Jocelyne Lew and Vinoth Manoharan for technical assistance and the members of the Clinical Research and Animal Care team at VIDO-InterVac, as well as Yanyun Huang and Dale Godson (Prairie Diagnostic Services Inc.). This work was supported by the University of Pittsburgh Medical Center. D.R.M. is funded by NIH (F32 AI152296), a Burroughs Wellcome Fund Postdoctoral Enrichment Program Award, and NIH NIAID (T32 AI007151). R.S.B. is supported by NIH (AI132178 and AI108197). Work in the Subramaniam laboratory is supported by a Canada Excellence Research Chair Award and a grant from Genome BC, Canada. Some monoclonal antibodies were generated by the UNC Protein Expression and Purification (PEP) core facility, which is funded by NIH (P30CA016086). D.S.D. R.S.B. C.-T.T. J.W.M. S.S. D.F. and W.L. conceived and designed the research. W.L. identified and characterized antibodies. X.L. and Z.S. helped to make libraries, characterized antibodies, and performed the cell fusion pseudovirus assays. C.C. made the RBD and ACE2. L.Z. made and characterized reagents. M.L.U. and E.C.P. characterized proteins and helped with the proteome assay. D.M. and A.D. performed the live virus neutralization assays. A.S. S.S.K. D.F. and S.L. performed the animal studies. A.B. S.C. K.L. D.M. S.S.S. X.Z. and S.S. produced and purified the S trimer, carried out the EM experiments, and analyzed the structure-related results. D.S.D. and W.L. wrote the first draft of the article. All authors discussed the results and contributed to the manuscript. W.L. C.C. Z.S. J.W.M. and D.S.D. are co-inventors of a patent, filed on March 12 by the University of Pittsburgh, related to ab8 described in this paper. Funding Information: We would like to thank the members of our group, Dontcho Jelev, Megan Shi, Cynthia Adams, Du-San Baek, Ye-Jin Kim, and Xiaojie Chu for their helpful discussions. We thank Dr. Kevin McCormick from the University of Pittsburgh, Rui Gong from the Institute of Virology in Wuhan, and Rachel Fong from Integral Molecular for helpful suggestions. We would also like to thank Jocelyne Lew and Vinoth Manoharan for technical assistance and the members of the Clinical Research and Animal Care team at VIDO-InterVac, as well as Yanyun Huang and Dale Godson (Prairie Diagnostic Services Inc.). This work was supported by the University of Pittsburgh Medical Center . D.R.M. is funded by NIH ( F32 AI152296 ), a Burroughs Wellcome Fund Postdoctoral Enrichment Program Award , and NIH NIAID ( T32 AI007151 ). R.S.B. is supported by NIH ( AI132178 and AI108197 ). Work in the Subramaniam laboratory is supported by a Canada Excellence Research Chair Award and a grant from Genome BC, Canada . Some monoclonal antibodies were generated by the UNC Protein Expression and Purification (PEP) core facility, which is funded by NIH ( P30CA016086 ). Publisher Copyright: {\textcopyright} 2020 Elsevier Inc.",
year = "2020",
month = oct,
day = "15",
doi = "10.1016/j.cell.2020.09.007",
language = "English (US)",
volume = "183",
pages = "429--441.e16",
journal = "Cell",
issn = "0092-8674",
publisher = "Cell Press",
number = "2",
}