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Journal Article Ppublish 10 citations

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

Hybrid immunity to SARS-CoV-2 arises from serological recall of IgG antibodies distinctly imprinted by infection or vaccination.

Cell Rep Med 5(8):101668

Authors: William 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

Affiliations

  • Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX, USA.
  • Department of Epidemiology, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Department of Biomedical Engineering, The University of Texas at Austin, Austin, TX, USA.
  • Basic Sciences Division and Computational Biology Program, Fred Hutchinson Cancer Center, Seattle, WA, USA.
  • Department of Chemical Engineering, The University of Texas at Austin, Austin, TX, USA.
  • Department of Microbiology and Immunology, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Department of Chemistry, The University of Texas at Austin, Austin, TX, USA.
  • Basic Sciences Division and Computational Biology Program, Fred Hutchinson Cancer Center, Seattle, WA, USA; Howard Hughes Medical Institute, Seattle, WA, USA.
  • Department of Epidemiology, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Department of Microbiology and Immunology, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Department of Chemical Engineering, The University of Texas at Austin, Austin, TX, USA.
  • Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX, USA.

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.

MeSH

Sars-Cov-2, Vaccines, Mental Recall, Biological Science Disciplines, Antibodies, Vaccination, Immunity, Severe Acute Respiratory Syndrome-Related Coronavirus, Infections, Plasma

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