8VIF

SARS-CoV-2 spike omicron (BA.1) ectodomain trimer in complex with SC27 Fab, local refinement

Summary for 8VIF

• Entry DOI: 10.2210/pdb8vif/pdb
• EMDB information: 43260
• Descriptor: SC27 Fab heavy chain, SC27 Fab light chain, Spike glycoprotein, ... (4 entities in total)
• Functional Keywords: sars-cov-2, coronavirus, s, spike, ba.1, omicron, rbd, covid-19, antibody, sc27, fab, virus, 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: 171012.70

Authors

Byrne, P.O.,McLellan, J.S. (deposition date: 2024-01-04, release date: 2024-07-24, Last modification date: 2025-05-21)

Primary citation

Voss, W.N.,Mallory, M.A.,Byrne, P.O.,Marchioni, J.M.,Knudson, S.A.,Powers, J.M.,Leist, S.R.,Dadonaite, B.,Townsend, D.R.,Kain, J.,Huang, Y.,Satterwhite, E.,Castillo, I.N.,Mattocks, M.,Paresi, C.,Munt, J.E.,Scobey, T.,Seeger, A.,Premkumar, L.,Bloom, J.D.,Georgiou, G.,McLellan, J.S.,Baric, R.S.,Lavinder, J.J.,Ippolito, G.C.
Hybrid immunity to SARS-CoV-2 arises from serological recall of IgG antibodies distinctly imprinted by infection or vaccination.
Cell Rep Med, 5:101668-101668, 2024

PubMed Abstract: We describe the molecular-level composition of polyclonal immunoglobulin G (IgG) anti-spike antibodies from ancestral severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, vaccination, or their combination ("hybrid immunity") at monoclonal resolution. Infection primarily triggers S2/N-terminal domain (NTD)-reactive antibodies, whereas vaccination mainly induces anti-receptor-binding domain (RBD) antibodies. This imprint persists after secondary exposures wherein >60% of ensuing hybrid immunity derives from the original IgG pool. Monoclonal constituents of the original IgG pool can increase breadth, affinity, and prevalence upon secondary exposures, as exemplified by the plasma antibody SC27. Following a breakthrough infection, vaccine-induced SC27 gained neutralization breadth and potency against SARS-CoV-2 variants and zoonotic viruses (half-maximal inhibitory concentration [IC] ∼0.1-1.75 nM) and increased its binding affinity to the protective RBD class 1/4 epitope (dissociation constant [K] < 5 pM). According to polyclonal escape analysis, SC27-like binding patterns are common in SARS-CoV-2 hybrid immunity. Our findings provide a detailed molecular definition of immunological imprinting and show that vaccination can produce class 1/4 (SC27-like) IgG antibodies circulating in the blood.

PubMed: 39094579
DOI: 10.1016/j.xcrm.2024.101668

Experimental method

ELECTRON MICROSCOPY (3.1 Å)