Publications Search

Search for publications by author
Search for publications by abstract keyword(s)

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


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 2021-05-31
Published Volume 13
Published Issue 1
Published Pages 1922134
Status Published in-print
DOI 10.1080/19420862.2021.1922134
URL link to publisher's version