tetano
Editor, Senior Moderator
MAbs
. Jan-Dec 2021;13(1):1922134.
doi: 10.1080/19420862.2021.1922134.
Potent SARS-CoV-2 binding and neutralization through maturation of iconic SARS-CoV-1 antibodies
Romain Rouet[SUP] 1 2 [/SUP], Ohan Mazigi[SUP] 1 2 [/SUP], Gregory J Walker[SUP] 3 4 [/SUP], David B Langley[SUP] 1 2 [/SUP], Meghna Sobti[SUP] 2 5 [/SUP], Peter Schofield[SUP] 1 2 [/SUP], Helen Lenthall[SUP] 1 2 [/SUP], Jennifer Jackson[SUP] 1 2 [/SUP], Stephanie Ubiparipovic[SUP] 1 2 [/SUP], Jake Y Henry[SUP] 1 2 [/SUP], Arunasingam Abayasingam[SUP] 3 6 [/SUP], Deborah Burnett[SUP] 1 2 [/SUP], Anthony Kelleher[SUP] 3 6 [/SUP], Robert Brink[SUP] 1 2 [/SUP], Rowena A Bull[SUP] 3 6 [/SUP], Stuart Turville[SUP] 3 6 [/SUP], Alastair G Stewart[SUP] 2 5 [/SUP], Christopher C Goodnow[SUP] 1 2 [/SUP], William D Rawlinson[SUP] 3 4 [/SUP], Daniel Christ[SUP] 1 2 [/SUP]
Affiliations
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.
Keywords: Monoclonal antibodies; SARS-CoV-2; antibody engineering; antibody maturation; phage display; structural studies.
. Jan-Dec 2021;13(1):1922134.
doi: 10.1080/19420862.2021.1922134.
Potent SARS-CoV-2 binding and neutralization through maturation of iconic SARS-CoV-1 antibodies
Romain Rouet[SUP] 1 2 [/SUP], Ohan Mazigi[SUP] 1 2 [/SUP], Gregory J Walker[SUP] 3 4 [/SUP], David B Langley[SUP] 1 2 [/SUP], Meghna Sobti[SUP] 2 5 [/SUP], Peter Schofield[SUP] 1 2 [/SUP], Helen Lenthall[SUP] 1 2 [/SUP], Jennifer Jackson[SUP] 1 2 [/SUP], Stephanie Ubiparipovic[SUP] 1 2 [/SUP], Jake Y Henry[SUP] 1 2 [/SUP], Arunasingam Abayasingam[SUP] 3 6 [/SUP], Deborah Burnett[SUP] 1 2 [/SUP], Anthony Kelleher[SUP] 3 6 [/SUP], Robert Brink[SUP] 1 2 [/SUP], Rowena A Bull[SUP] 3 6 [/SUP], Stuart Turville[SUP] 3 6 [/SUP], Alastair G Stewart[SUP] 2 5 [/SUP], Christopher C Goodnow[SUP] 1 2 [/SUP], William D Rawlinson[SUP] 3 4 [/SUP], Daniel Christ[SUP] 1 2 [/SUP]
Affiliations
- PMID: 34024246
- DOI: 10.1080/19420862.2021.1922134
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.
Keywords: Monoclonal antibodies; SARS-CoV-2; antibody engineering; antibody maturation; phage display; structural studies.