Broadly neutralizing SARS-CoV-2 antibodies through epitope-based selection from convalescent patients

Romain Rouet (), Jake Y. Henry, Matt D. Johansen, Meghna Sobti, Harikrishnan Balachandran, David B. Langley, Gregory J. Walker, Helen Lenthall, Jennifer Jackson, Stephanie Ubiparipovic, Ohan Mazigi, Peter Schofield, Deborah L. Burnett, Simon H. J. Brown, Marianne Martinello, Bernard Hudson, Nicole Gilroy, Jeffrey J. Post, Anthony Kelleher, Hans-Martin Jäck, Christopher C. Goodnow, Stuart G. Turville, William D. Rawlinson, Rowena A. Bull, Alastair G. Stewart, Philip M. Hansbro and Daniel Christ ()
Additional contact information
Romain Rouet: Garvan Institute of Medical Research
Jake Y. Henry: Garvan Institute of Medical Research
Matt D. Johansen: Centenary Institute and University of Technology Sydney
Meghna Sobti: Faculty of Medicine
Harikrishnan Balachandran: Faculty of Medicine
David B. Langley: Garvan Institute of Medical Research
Gregory J. Walker: Faculty of Medicine
Helen Lenthall: Garvan Institute of Medical Research
Jennifer Jackson: Garvan Institute of Medical Research
Stephanie Ubiparipovic: Garvan Institute of Medical Research
Ohan Mazigi: Garvan Institute of Medical Research
Peter Schofield: Garvan Institute of Medical Research
Deborah L. Burnett: Garvan Institute of Medical Research
Simon H. J. Brown: University of Wollongong
Marianne Martinello: Faculty of Medicine
Bernard Hudson: Royal North Shore Hospital
Nicole Gilroy: Westmead Hospital
Jeffrey J. Post: Prince of Wales Hospital
Anthony Kelleher: Faculty of Medicine
Hans-Martin Jäck: Friedrich-Alexander University Erlangen-Nürnberg and University Hospital Erlangen
Christopher C. Goodnow: Garvan Institute of Medical Research
Stuart G. Turville: Faculty of Medicine
William D. Rawlinson: Faculty of Medicine
Rowena A. Bull: Faculty of Medicine
Alastair G. Stewart: Faculty of Medicine
Philip M. Hansbro: Prince of Wales Hospital
Daniel Christ: Garvan Institute of Medical Research

Nature Communications, 2023, vol. 14, issue 1, 1-13

Abstract: Abstract Emerging variants of concern (VOCs) are threatening to limit the effectiveness of SARS-CoV-2 monoclonal antibodies and vaccines currently used in clinical practice; broadly neutralizing antibodies and strategies for their identification are therefore urgently required. Here we demonstrate that broadly neutralizing antibodies can be isolated from peripheral blood mononuclear cells of convalescent patients using SARS-CoV-2 receptor binding domains carrying epitope-specific mutations. This is exemplified by two human antibodies, GAR05, binding to epitope class 1, and GAR12, binding to a new epitope class 6 (located between class 3 and 5). Both antibodies broadly neutralize VOCs, exceeding the potency of the clinical monoclonal sotrovimab (S309) by orders of magnitude. They also provide prophylactic and therapeutic in vivo protection of female hACE2 mice against viral challenge. Our results indicate that exposure to SARS-CoV-2 induces antibodies that maintain broad neutralization against emerging VOCs using two unique strategies: either by targeting the divergent class 1 epitope in a manner resistant to VOCs (ACE2 mimicry, as illustrated by GAR05 and mAbs P2C-1F11/S2K14); or alternatively, by targeting rare and highly conserved epitopes, such as the new class 6 epitope identified here (as illustrated by GAR12). Our results provide guidance for next generation monoclonal antibody development and vaccine design.

Date: 2023
References: View references in EconPapers View complete reference list from CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/s41467-023-36295-5 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:14:y:2023:i:1:d:10.1038_s41467-023-36295-5

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

DOI: 10.1038/s41467-023-36295-5

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 ().