ジャーナル: MAbs / 年: 2021 タイトル: Potent SARS-CoV-2 binding and neutralization through maturation of iconic SARS-CoV-1 antibodies. 著者: Romain Rouet / Ohan Mazigi / Gregory J Walker / David B Langley / Meghna Sobti / Peter Schofield / Helen Lenthall / Jennifer Jackson / Stephanie Ubiparipovic / Jake Y Henry / Arunasingam ...著者: Romain Rouet / Ohan Mazigi / Gregory J Walker / David B Langley / Meghna Sobti / Peter Schofield / Helen Lenthall / Jennifer Jackson / Stephanie Ubiparipovic / Jake Y Henry / Arunasingam Abayasingam / Deborah Burnett / Anthony Kelleher / Robert Brink / Rowena A Bull / Stuart Turville / Alastair G Stewart / Christopher C Goodnow / William D Rawlinson / Daniel Christ / 要旨: 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 ...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.
H: Fab heavy chain of CR3014-C8 antibody L: Fab light chain of CR3014-C8 antibody C: Spike glycoprotein A: Fab heavy chain of CR3022-B6 antibody B: Fab light chain of CR3022-B6 antibody ヘテロ分子
解像度: 2.83→49.38 Å / Cor.coef. Fo:Fc: 0.909 / Cor.coef. Fo:Fc free: 0.745 / WRfactor Rfree: 0.3135 / WRfactor Rwork: 0.2378 / FOM work R set: 0.709 / SU B: 47.881 / SU ML: 0.421 / SU R Cruickshank DPI: 0.383 / SU Rfree: 0.4965 / 交差検証法: THROUGHOUT / σ(F): 0 / ESU R Free: 0.497 / 立体化学のターゲット値: MAXIMUM LIKELIHOOD 詳細: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS U VALUES : WITH TLS ADDED
Rfactor
反射数
%反射
Selection details
Rfree
0.3356
1462
5.1 %
RANDOM
Rwork
0.2514
-
-
-
obs
0.2558
27165
99.62 %
-
溶媒の処理
イオンプローブ半径: 0.8 Å / 減衰半径: 0.8 Å / VDWプローブ半径: 1.2 Å / 溶媒モデル: MASK