Potent and protective IGHV3-53/3-66 public antibodies and their shared escape mutant on the spike of SARS-CoV-2

Qi Zhang, Bin Ju, Jiwan Ge, Jasper Fuk-Woo Chan, Lin Cheng, Ruoke Wang, Weijin Huang, Mengqi Fang, Peng Chen, Bing Zhou, Shuo Song, Sisi Shan, Baohua Yan, Senyan Zhang, Xiangyang Ge, Jiazhen Yu, Juanjuan Zhao, Haiyan Wang, Li Liu, Qining Lv, Lili Fu, Xuanling Shi, Kwok Yung Yuen, Lei Liu, Youchun Wang (), Zhiwei Chen (), Linqi Zhang (), Xinquan Wang () and Zheng Zhang ()
Additional contact information
Qi Zhang: Tsinghua University
Bin Ju: Shenzhen Third People’s Hospital; The Second Affiliated Hospital, School of Medicine, Southern University of Science and Technology
Jiwan Ge: Tsinghua University
Jasper Fuk-Woo Chan: The University of Hong Kong
Lin Cheng: Shenzhen Third People’s Hospital; The Second Affiliated Hospital, School of Medicine, Southern University of Science and Technology
Ruoke Wang: Tsinghua University
Weijin Huang: National Institutes for Food and Drug Control
Mengqi Fang: Tsinghua University
Peng Chen: Tsinghua University
Bing Zhou: Shenzhen Third People’s Hospital; The Second Affiliated Hospital, School of Medicine, Southern University of Science and Technology
Shuo Song: Shenzhen Third People’s Hospital; The Second Affiliated Hospital, School of Medicine, Southern University of Science and Technology
Sisi Shan: Tsinghua University
Baohua Yan: Tsinghua University
Senyan Zhang: Tsinghua University
Xiangyang Ge: Shenzhen Third People’s Hospital; The Second Affiliated Hospital, School of Medicine, Southern University of Science and Technology
Jiazhen Yu: Shenzhen Third People’s Hospital; The Second Affiliated Hospital, School of Medicine, Southern University of Science and Technology
Juanjuan Zhao: Shenzhen Third People’s Hospital; The Second Affiliated Hospital, School of Medicine, Southern University of Science and Technology
Haiyan Wang: Shenzhen Third People’s Hospital; The Second Affiliated Hospital, School of Medicine, Southern University of Science and Technology
Li Liu: The University of Hong Kong
Qining Lv: Tsinghua University
Lili Fu: Tsinghua University
Xuanling Shi: Tsinghua University
Kwok Yung Yuen: The University of Hong Kong
Lei Liu: Shenzhen Third People’s Hospital; The Second Affiliated Hospital, School of Medicine, Southern University of Science and Technology
Youchun Wang: National Institutes for Food and Drug Control
Zhiwei Chen: The University of Hong Kong
Linqi Zhang: Tsinghua University
Xinquan Wang: Tsinghua University
Zheng Zhang: Shenzhen Third People’s Hospital; The Second Affiliated Hospital, School of Medicine, Southern University of Science and Technology

Nature Communications, 2021, vol. 12, issue 1, 1-12

Abstract: Abstract Neutralizing antibodies (nAbs) to SARS-CoV-2 hold powerful potentials for clinical interventions against COVID-19 disease. However, their common genetic and biologic features remain elusive. Here we interrogate a total of 165 antibodies from eight COVID-19 patients, and find that potent nAbs from different patients have disproportionally high representation of IGHV3-53/3-66 usage, and therefore termed as public antibodies. Crystal structural comparison of these antibodies reveals they share similar angle of approach to RBD, overlap in buried surface and binding residues on RBD, and have substantial spatial clash with receptor angiotensin-converting enzyme-2 (ACE2) in binding to RBD. Site-directed mutagenesis confirms these common binding features although some minor differences are found. One representative antibody, P5A-3C8, demonstrates extraordinarily protective efficacy in a golden Syrian hamster model against SARS-CoV-2 infection. However, virus escape analysis identifies a single natural mutation in RBD, namely K417N found in B.1.351 variant from South Africa, abolished the neutralizing activity of these public antibodies. The discovery of public antibodies and shared escape mutation highlight the intricate relationship between antibody response and SARS-CoV-2, and provide critical reference for the development of antibody and vaccine strategies to overcome the antigenic variation of SARS-CoV-2.

Date: 2021
References: Add references at CitEc
Citations: View citations in EconPapers (8)

Downloads: (external link)
https://www.nature.com/articles/s41467-021-24514-w Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-24514-w

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-021-24514-w

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().