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 SH, Martinello M, Hudson B, Gilroy N, Post JJ, Kelleher A, Jäck HM, Goodnow CC, Turville SG, Rawlinson WD, Bull RA, Stewart AG, Hansbro PM, Christ D (2023)

Publication Type: Journal article

Publication year: 2023

Journal

Nature Communications Nature Publishing Group: Nature Communications

Book Volume: 14

Article Number: 687

Journal Issue: 1

DOI: 10.1038/s41467-023-36295-5

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.

Authors with CRIS profile

Hans-Martin Jäck Department of Molecular Immunology

Involved external institutions

Garvan Institute of Medical Research AU Australia (AU) University of Technology Sydney (UTS) AU Australia (AU) University of New South Wales (UNSW) AU Australia (AU) University of Wollongong (UOW) AU Australia (AU) Royal North Shore Hospital (RNSH) AU Australia (AU) Westmead Hospital AU Australia (AU) Prince of Wales Hospital (POWH) AU Australia (AU)

How to cite

APA:

Rouet, R., Henry, J.Y., Johansen, M.D., Sobti, M., Balachandran, H., Langley, D.B.,... Christ, D. (2023). Broadly neutralizing SARS-CoV-2 antibodies through epitope-based selection from convalescent patients. Nature Communications, 14(1). https://dx.doi.org/10.1038/s41467-023-36295-5

MLA:

Rouet, Romain, et al. "Broadly neutralizing SARS-CoV-2 antibodies through epitope-based selection from convalescent patients." Nature Communications 14.1 (2023).

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