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-Structure paper
タイトル | Potent SARS-CoV-2 binding and neutralization through maturation of iconic SARS-CoV-1 antibodies. |
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ジャーナル・号・ページ | MAbs, Vol. 13, Issue 1, Page 1922134, Year 2021 |
掲載日 | 2021年5月28日 |
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 / |
PubMed 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. |
リンク | MAbs / PubMed:34024246 / PubMed Central |
手法 | EM (単粒子) / X線回折 |
解像度 | 1.69 - 4.6 Å |
構造データ | EMDB-23111: EMDB-23112: EMDB-23113: PDB-7kza: PDB-7kzb: PDB-7kzc: |
化合物 | ChemComp-CL: ChemComp-GOL: ChemComp-NA: ChemComp-PO4: ChemComp-HOH: |
由来 |
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キーワード | IMMUNE SYSTEM / COVID19 / SARS-CoV2 / antibody / ANTIVIRAL PROTEIN / VIRAL PROTEIN/Immune System / VIRAL PROTEIN-Immune System complex |