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.
|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|
|URL link to publisher's version||https://www.ncbi.nlm.nih.gov/pubmed/34024246|