8V4F

Model and map from local refinement of a CAB-A17 - Omicron Ba.1 spike complex

Summary for 8V4F

• Entry DOI: 10.2210/pdb8v4f/pdb
• EMDB information: 42970
• Descriptor: CAB-A17 variable heavy-chain, CAB-A17 variable light chain, Spike protein S1 (3 entities in total)
• Functional Keywords: sars-cov-2, spike, rbd, antibody, fab, viral protein, viral protein-immune system complex, viral protein/immune system
• Biological source: Homo sapiens; More
• Total number of polymer chains: 3
• Total formula weight: 46290.72

Authors

Hallberg, B.M.,Das, H. (deposition date: 2023-11-29, release date: 2024-06-05, Last modification date: 2024-10-23)

Primary citation

Sheward, D.J.,Pushparaj, P.,Das, H.,Greaney, A.J.,Kim, C.,Kim, S.,Hanke, L.,Hyllner, E.,Dyrdak, R.,Lee, J.,Dopico, X.C.,Dosenovic, P.,Peacock, T.P.,McInerney, G.M.,Albert, J.,Corcoran, M.,Bloom, J.D.,Murrell, B.,Karlsson Hedestam, G.B.,Hallberg, B.M.
Structural basis of broad SARS-CoV-2 cross-neutralization by affinity-matured public antibodies.
Cell Rep Med, 5:101577-101577, 2024

PubMed Abstract: 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.

PubMed: 38761799
DOI: 10.1016/j.xcrm.2024.101577

Experimental method

ELECTRON MICROSCOPY (2.68 Å)