Imprinted antibody responses against SARS-CoV-2 Omicron sublineages

Science. 2022 Nov 11;378(6620):619-627. doi: 10.1126/science.adc9127. Epub 2022 Oct 20.


Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron sublineages carry distinct spike mutations resulting in escape from antibodies induced by previous infection or vaccination. We show that hybrid immunity or vaccine boosters elicit plasma-neutralizing antibodies against Omicron BA.1, BA.2, BA.2.12.1, and BA.4/5, and that breakthrough infections, but not vaccination alone, induce neutralizing antibodies in the nasal mucosa. Consistent with immunological imprinting, most antibodies derived from memory B cells or plasma cells of Omicron breakthrough cases cross-react with the Wuhan-Hu-1, BA.1, BA.2, and BA.4/5 receptor-binding domains, whereas Omicron primary infections elicit B cells of narrow specificity up to 6 months after infection. Although most clinical antibodies have reduced neutralization of Omicron, we identified an ultrapotent pan-variant-neutralizing antibody that is a strong candidate for clinical development.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Neutralizing* / immunology
  • Antibodies, Viral* / immunology
  • Antibody Formation*
  • COVID-19* / immunology
  • Humans
  • Immune Evasion*
  • Immunologic Memory
  • Memory B Cells / immunology
  • Neutralization Tests
  • SARS-CoV-2* / genetics
  • SARS-CoV-2* / immunology
  • Spike Glycoprotein, Coronavirus*


  • Antibodies, Neutralizing
  • Antibodies, Viral
  • spike protein, SARS-CoV-2
  • Spike Glycoprotein, Coronavirus

Supplementary concepts

  • SARS-CoV-2 variants