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Imprinted antibody responses against SARS-CoV-2 Omicron sublineages


Abstract

SARS-CoV-2 Omicron sublineages carry distinct spike mutations and represent an antigenic shift resulting in escape from antibodies induced by previous infection or vaccination. We show that hybrid immunity or vaccine boosters result in potent plasma neutralizing activity against Omicron BA.1 and BA.2 and that breakthrough infections, but not vaccination-only, induce neutralizing activity 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 and BA.2 receptor-binding domains whereas Omicron primary infections elicit B cells of narrow specificity. While most clinical antibodies have reduced neutralization of Omicron, we identified an ultrapotent pan-variant antibody, that is unaffected by any Omicron lineage spike mutations and is a strong candidate for clinical development.

Abstract

SARS-CoV-2 Omicron sublineages carry distinct spike mutations and represent an antigenic shift resulting in escape from antibodies induced by previous infection or vaccination. We show that hybrid immunity or vaccine boosters result in potent plasma neutralizing activity against Omicron BA.1 and BA.2 and that breakthrough infections, but not vaccination-only, induce neutralizing activity 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 and BA.2 receptor-binding domains whereas Omicron primary infections elicit B cells of narrow specificity. While most clinical antibodies have reduced neutralization of Omicron, we identified an ultrapotent pan-variant antibody, that is unaffected by any Omicron lineage spike mutations and is a strong candidate for clinical development.

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Item Type:Working Paper
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Clinical Pharmacology and Toxicology
Dewey Decimal Classification:610 Medicine & health
Scopus Subject Areas:Health Sciences > Multidisciplinary
Language:English
Date:October 2022
Deposited On:13 Jan 2023 16:05
Last Modified:06 Jun 2024 07:45
Series Name:bioRxiv
ISSN:2164-7844
Additional Information:Version 1 am 10.05.2022 submittet; Version 2 und 3 im Juni 2022 überarbeitet; Version 4 am 22.08.2022 überarbeitet.
OA Status:Green
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1101/2022.05.08.491108
Related URLs:https://pubmed.ncbi.nlm.nih.gov/36264829/
https://www.science.org/doi/10.1126/science.adc9127
https://www.zora.uzh.ch/id/eprint/226753/
  • Content: Updated Version
  • Language: English
  • Description: Version 4 vom 22.08.2022
  • Licence: Creative Commons: Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)
  • Content: Published Version
  • Language: English
  • Description: Version 1 vom 10.05.2022
  • Licence: Creative Commons: Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)