RT Journal Article
SR Electronic
T1 An Engineered Antibody with Broad Protective Efficacy in Murine Models of SARS and COVID-19
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.11.17.385500
DO 10.1101/2020.11.17.385500
A1 C. Garrett Rappazzo
A1 Longping V. Tse
A1 Chengzi I. Kaku
A1 Daniel Wrapp
A1 Mrunal Sakharkar
A1 Deli Huang
A1 Laura M. Deveau
A1 Thomas J. Yockachonis
A1 Andrew S. Herbert
A1 Michael B. Battles
A1 Cecilia M. O’Brien
A1 Michael E. Brown
A1 James C. Geoghegan
A1 Jonathan Belk
A1 Linghang Peng
A1 Linlin Yang
A1 Trevor D. Scobey
A1 Dennis R. Burton
A1 David Nemazee
A1 John M. Dye
A1 James E. Voss
A1 Bronwyn M. Gunn
A1 Jason S. McLellan
A1 Ralph S. Baric
A1 Lisa E. Gralinski
A1 Laura M. Walker
YR 2020
UL http://biorxiv.org/content/early/2020/11/17/2020.11.17.385500.abstract
AB The recurrent zoonotic spillover of coronaviruses (CoVs) into the human population underscores the need for broadly active countermeasures. Here, we employed a directed evolution approach to engineer three SARS-CoV-2 antibodies for enhanced neutralization breadth and potency. One of the affinity-matured variants, ADG-2, displays strong binding activity to a large panel of sarbecovirus receptor binding domains (RBDs) and neutralizes representative epidemic sarbecoviruses with remarkable potency. Structural and biochemical studies demonstrate that ADG-2 employs a unique angle of approach to recognize a highly conserved epitope overlapping the receptor binding site. In murine models of SARS-CoV and SARS-CoV-2 infection, passive transfer of ADG-2 provided complete protection against respiratory burden, viral replication in the lungs, and lung pathology. Altogether, ADG-2 represents a promising broad-spectrum therapeutic candidate for the treatment and prevention of SARS-CoV-2 and future emerging SARS-like CoVs.Competing Interest StatementC.G.R, C.I.K, M.S., L.M.D., M.B.B., M.E.B., J.C.G., and L.M.W. are employees of Adimab, LLC and may hold shares in Adimab, LLC. L.M.W. is an employee of Adagio Therapeutics Inc. and holds shares in Adagio Therapeutics Inc. D.R.B. is on the SAB of Adimab, LLC and Adagio Therapeutics Inc. and holds shares in Adimab, LLC.