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Potent SARS-CoV-2 binding and neutralization through maturation of iconic SARS-CoV-1 antibodies

Abstract

Antibodies against coronavirus spike protein potently protect against infection and disease, but whether such protection can be extended to variant coronaviruses is unclear. This is exemplified by a set of iconic and well-characterized monoclonal antibodies developed after the 2003 SARS outbreak, including mAbs m396, CR3022, CR3014 and 80R, which potently neutralize SARS-CoV-1, but not SARS-CoV-2. Here, we explore antibody engineering strategies to change and broaden their specificity, enabling nanomolar binding and potent neutralization of SARS-CoV-2. Intriguingly, while many of the matured clones maintained specificity of the parental antibody, new specificities were also observed, which was further confirmed by X-ray crystallography and cryo-electron microscopy, indicating that a limited set of VH antibody domains can give rise to variants targeting diverse epitopes, when paired with a diverse VL repertoire. Our findings open up over 15 years of antibody development efforts against SARS-CoV-1 to the SARS-CoV-2 field and outline general principles for the maturation of antibody specificity against emerging viruses.

Type Journal
Authors Rouet, R. Mazigi, O. Walker, G. J. Langley, D. B. Sobti, M. Schofield, P. Lenthall, H. Jackson, J. Ubiparipovic, S. Henry, J. Y. Abayasingam, A. Burnett, D. Kelleher, A. Brink, R. Bull, R. A. Turville, S. Stewart, A. G. Goodnow, C. C. Rawlinson, W. D. Christ, D.
Responsible Garvan Author Prof Daniel Christ
Publisher Name mAbs
Published Date 2021-05-25
Published Volume 13
Published Issue 1
Published Pages 1922134
Status Always Electronic
DOI 10.1080/19420862.2021.1922134