RT Journal Article
SR Electronic
T1 Engineering SARS-CoV-2 neutralizing antibodies for increased potency and reduced viral escape
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2022.01.06.475303
DO 10.1101/2022.01.06.475303
A1 Fangzhu Zhao
A1 Celina Keating
A1 Gabriel Ozorowski
A1 Namir Shaabani
A1 Irene M. Francino-Urdaniz
A1 Shawn Barman
A1 Oliver Limbo
A1 Alison Burns
A1 Panpan Zhou
A1 Michael J. Ricciardi
A1 Jordan Woehl
A1 Quoc Tran
A1 Hannah L. Turner
A1 Linghang Peng
A1 Deli Huang
A1 David Nemazee
A1 Raiees Andrabi
A1 Devin Sok
A1 John R. Teijaro
A1 Timothy A. Whitehead
A1 Andrew B. Ward
A1 Dennis R. Burton
A1 Joseph G. Jardine
YR 2022
UL http://biorxiv.org/content/early/2022/01/07/2022.01.06.475303.abstract
AB The rapid spread of SARS-CoV-2 variants poses a constant threat of escape from monoclonal antibody and vaccine countermeasures. Mutations in the ACE2 receptor binding site on the surface S protein have been shown to disrupt antibody binding and prevent viral neutralization. Here, we use a directed evolution-based approach to engineer three neutralizing antibodies for enhanced binding to S protein. The engineered antibodies showed increased in vitro functional activity in terms of neutralization potency and/or breadth of neutralization against viral variants. Deep mutational scanning revealed that higher binding affinity reduced the total number of viral escape mutations. Studies in the Syrian hamster model showed two examples where the affinity matured antibody provided superior protection compared to the parental antibody. These data suggest that monoclonal antibodies for anti-viral indications could benefit from in vitro affinity maturation to reduce viral escape pathways and appropriate affinity maturation in vaccine immunization could help resist viral variation.Competing Interest StatementJ.G.J., D.R.B., and F.Z. are listed as inventors on pending patent applications describing the engineered SARS-CoV-2 neutralizing antibodies.