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

Rouet, R; Henry, JY; Johansen, MD; Sobti, M; Balachandran, H; Langley, DB; Walker, GJ; Lenthall, H; Jackson, J; Ubiparipovic, S; Mazigi, O; Schofield, P; Burnett, DL; Brown, SHJ; Martinello, M; Hudson, B; Gilroy, N; Post, JJ; Kelleher, A; Jäck, H-M; Goodnow, CC; Turville, SG; Rawlinson, WD; Bull, RA; Stewart, AG; Hansbro, PM; Christ, D

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

Rouet, R Henry, JY Johansen, MD Sobti, M Balachandran, H Langley, DB Walker, GJ Lenthall, H Jackson, J Ubiparipovic, S Mazigi, O Schofield, P Burnett, DL Brown, SHJ Martinello, M Hudson, B Gilroy, N Post, JJ Kelleher, A Jäck, H-M Goodnow, CC Turville, SG Rawlinson, WD Bull, RA Stewart, AG Hansbro, PM Christ, D

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Publisher:: Springer Nature
Publication Type:: Journal Article
Citation:: Nat Commun, 2023, 14, (1), pp. 687
Issue Date:: 2023-02-08

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Field	Value	Language
dc.contributor.author	Rouet, R
dc.contributor.author	Henry, JY
dc.contributor.author	Johansen, MD
dc.contributor.author	Sobti, M
dc.contributor.author	Balachandran, H
dc.contributor.author	Langley, DB
dc.contributor.author	Walker, GJ
dc.contributor.author	Lenthall, H
dc.contributor.author	Jackson, J
dc.contributor.author	Ubiparipovic, S
dc.contributor.author	Mazigi, O
dc.contributor.author	Schofield, P
dc.contributor.author	Burnett, DL
dc.contributor.author	Brown, SHJ
dc.contributor.author	Martinello, M
dc.contributor.author	Hudson, B
dc.contributor.author	Gilroy, N
dc.contributor.author	Post, JJ
dc.contributor.author	Kelleher, A
dc.contributor.author	Jäck, H-M
dc.contributor.author	Goodnow, CC
dc.contributor.author	Turville, SG
dc.contributor.author	Rawlinson, WD
dc.contributor.author	Bull, RA
dc.contributor.author	Stewart, AG
dc.contributor.author	Hansbro, PM
dc.contributor.author	Christ, D
dc.date.accessioned	2023-08-09T05:57:08Z
dc.date.available	2023-01-25
dc.date.available	2023-08-09T05:57:08Z
dc.date.issued	2023-02-08
dc.identifier.citation	Nat Commun, 2023, 14, (1), pp. 687
dc.identifier.issn	2041-1723
dc.identifier.issn	2041-1723
dc.identifier.uri	http://hdl.handle.net/10453/171770
dc.description.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.
dc.format	Electronic
dc.language	eng
dc.publisher	Springer Nature
dc.relation	http://purl.org/au-research/grants/nhmrc/1175134
dc.relation.ispartof	Nat Commun
dc.relation.isbasedon	10.1038/s41467-023-36295-5
dc.rights	info:eu-repo/semantics/restrictedAccess
dc.subject.mesh	Humans
dc.subject.mesh	Female
dc.subject.mesh	Animals
dc.subject.mesh	Mice
dc.subject.mesh	SARS-CoV-2
dc.subject.mesh	Broadly Neutralizing Antibodies
dc.subject.mesh	Leukocytes, Mononuclear
dc.subject.mesh	COVID-19
dc.subject.mesh	Antibodies, Viral
dc.subject.mesh	Antibodies, Monoclonal
dc.subject.mesh	Antibodies, Neutralizing
dc.subject.mesh	Epitopes
dc.subject.mesh	Spike Glycoprotein, Coronavirus
dc.subject.mesh	Neutralization Tests
dc.subject.mesh	Leukocytes, Mononuclear
dc.subject.mesh	Animals
dc.subject.mesh	Humans
dc.subject.mesh	Mice
dc.subject.mesh	Antibodies, Monoclonal
dc.subject.mesh	Antibodies, Viral
dc.subject.mesh	Epitopes
dc.subject.mesh	Neutralization Tests
dc.subject.mesh	Female
dc.subject.mesh	Antibodies, Neutralizing
dc.subject.mesh	Spike Glycoprotein, Coronavirus
dc.subject.mesh	Broadly Neutralizing Antibodies
dc.subject.mesh	COVID-19
dc.subject.mesh	SARS-CoV-2
dc.subject.mesh	Humans
dc.subject.mesh	Female
dc.subject.mesh	Animals
dc.subject.mesh	Mice
dc.subject.mesh	SARS-CoV-2
dc.subject.mesh	Broadly Neutralizing Antibodies
dc.subject.mesh	Leukocytes, Mononuclear
dc.subject.mesh	COVID-19
dc.subject.mesh	Antibodies, Viral
dc.subject.mesh	Antibodies, Monoclonal
dc.subject.mesh	Antibodies, Neutralizing
dc.subject.mesh	Epitopes
dc.subject.mesh	Spike Glycoprotein, Coronavirus
dc.subject.mesh	Neutralization Tests
dc.title	Broadly neutralizing SARS-CoV-2 antibodies through epitope-based selection from convalescent patients.
dc.type	Journal Article
utslib.citation.volume	14
utslib.location.activity	England
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Life Sciences
pubs.organisational-group	/University of Technology Sydney/Strength - CFI - Centre for Inflammation
utslib.copyright.status	in_progress	*
dc.date.updated	2023-08-09T05:57:03Z
pubs.issue	1
pubs.publication-status	Published online
pubs.volume	14
utslib.citation.issue	1

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.

Please use this identifier to cite or link to this item:

http://hdl.handle.net/10453/171770