新たに発見された抗体がCOVID-19の全バリアントを防御(Newly Discovered Antibody Protects Against All COVID-19 Variants)

2024-09-03 テキサス大学オースチン校(UT Austin)

<関連情報>

• https://news.utexas.edu/2024/09/03/newly-discovered-antibody-protects-against-all-covid-19-variants/
• https://www.cell.com/cell-reports-medicine/fulltext/S2666-3791(24)00382-3

SARS-CoV-2に対するハイブリッド免疫は、感染またはワクチン接種によって明確に刷り込まれたIgG抗体の血清学的想起から生じる Hybrid immunity to SARS-CoV-2 arises from serological recall of IgG antibodies distinctly imprinted by infection or vaccination

William N. Voss,Michael L. Mallory,Patrick O. Byrne, … , Ralph S. Baric,Jason J. Lavinder,Gregory C. Ippolito
Cell Reports Medicine  Published:August 1, 2024
DOI:https://doi.org/10.1016/j.xcrm.2024.101668

Graphical abstract

Highlights

• Infection and vaccination imprint distinct IgG responses at the molecular level
• Immunological imprinting varies between infection (S2/NTD) and vaccination (RBD)
• Over 60% of the IgG recall in hybrid immunity originates from the initial exposure
• Hybrid immune IgG plasma mAbs have superior neutralization potency and breadth

Summary

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 [IC₅₀] ∼0.1–1.75 nM) and increased its binding affinity to the protective RBD class 1/4 epitope (dissociation constant [K_D] < 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.