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-Structure paper
タイトル | Structural basis of broad SARS-CoV-2 cross-neutralization by affinity-matured public antibodies. |
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ジャーナル・号・ページ | Cell Rep Med, Vol. 5, Issue 6, Page 101577, Year 2024 |
掲載日 | 2024年5月15日 |
![]() | Daniel J Sheward / Pradeepa Pushparaj / Hrishikesh Das / Allison J Greaney / Changil Kim / Sungyong Kim / Leo Hanke / Erik Hyllner / Robert Dyrdak / Jimin Lee / Xaquin Castro Dopico / Pia Dosenovic / Thomas P Peacock / Gerald M McInerney / Jan Albert / Martin Corcoran / Jesse D Bloom / Ben Murrell / Gunilla B Karlsson Hedestam / B Martin Hällberg / ![]() ![]() ![]() ![]() ![]() |
PubMed 要旨 | Descendants of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant now account for almost all SARS-CoV-2 infections. The Omicron variant and its sublineages have spike ...Descendants of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant now account for almost all SARS-CoV-2 infections. The Omicron variant and its sublineages have spike glycoproteins that are highly diverged from the pandemic founder and first-generation vaccine strain, resulting in significant evasion from monoclonal antibody therapeutics and vaccines. Understanding how commonly elicited antibodies can broaden to cross-neutralize escape variants is crucial. We isolate IGHV3-53, using "public" monoclonal antibodies (mAbs) from an individual 7 months post infection with the ancestral virus and identify antibodies that exhibit potent and broad cross-neutralization, extending to the BA.1, BA.2, and BA.4/BA.5 sublineages of Omicron. Deep mutational scanning reveals these mAbs' high resistance to viral escape. Structural analysis via cryoelectron microscopy of a representative broadly neutralizing antibody, CAB-A17, in complex with the Omicron BA.1 spike highlights the structural underpinnings of this broad neutralization. By reintroducing somatic hypermutations into a germline-reverted CAB-A17, we delineate the role of affinity maturation in the development of cross-neutralization by a public class of antibodies. |
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手法 | EM (単粒子) |
解像度 | 2.68 Å |
構造データ | EMDB-16375, PDB-8c0y: EMDB-42970, PDB-8v4f: |
由来 |
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![]() | VIRAL PROTEIN / Antibody / Spike / Complex / VIRAL PROTEIN/IMMUNE SYSTEM / SARS-CoV-2 / RBD / Fab / VIRAL PROTEIN-IMMUNE SYSTEM complex |