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TitleHybrid immunity to SARS-CoV-2 arises from serological recall of IgG antibodies distinctly imprinted by infection or vaccination.
Journal, issue, pagesCell Rep Med, Vol. 5, Issue 8, Page 101668, Year 2024
Publish dateAug 20, 2024
AuthorsWilliam N Voss / Michael A Mallory / Patrick O Byrne / Jeffrey M Marchioni / Sean A Knudson / John M Powers / Sarah R Leist / Bernadeta Dadonaite / Douglas R Townsend / Jessica Kain / Yimin Huang / Ed Satterwhite / Izabella N Castillo / Melissa Mattocks / Chelsea Paresi / Jennifer E Munt / Trevor Scobey / Allison Seeger / Lakshmanane Premkumar / Jesse D Bloom / George Georgiou / Jason S McLellan / Ralph S Baric / Jason J Lavinder / Gregory C Ippolito /
PubMed AbstractWe 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, ...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.
External linksCell Rep Med / PubMed:39094579 / PubMed Central
MethodsEM (single particle)
Resolution2.6 - 3.1 Å
Structure data

EMDB-43250: SARS-CoV-2 spike omicron (BA.1) ectodomain trimer in complex with SC27 Fab, global refinement
Method: EM (single particle) / Resolution: 2.6 Å

43260

8vif

EMDB-43260, PDB-8vif:
SARS-CoV-2 spike omicron (BA.1) ectodomain trimer in complex with SC27 Fab, local refinement
Method: EM (single particle) / Resolution: 3.1 Å

EMDB-43261: SARS-CoV-2 spike omicron (BA.1) ectodomain dimer-of-trimers in complex with SC27 Fab, global refinement
Method: EM (single particle) / Resolution: 3.0 Å

43315

8vke

EMDB-43315, PDB-8vke:
SARS-CoV-2 spike omicron (BA.1) RBD ectodomain dimer-of-trimers in complex with SC27 Fabs
Method: EM (single particle) / Resolution: 3.1 Å

Chemicals

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose

Source
  • severe acute respiratory syndrome coronavirus 2
  • homo sapiens (human)
KeywordsVIRAL PROTEIN/IMMUNE SYSTEM / SARS-CoV-2 / coronavirus / S / spike / BA.1 / omicron / RBD / COVID-19 / antibody / SC27 / Fab / virus / viral protein / VIRAL PROTEIN-IMMUNE SYSTEM complex

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