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Age-associated B cells predict impaired humoral immunity after COVID-19 vaccination in patients receiving immune checkpoint blockade

Author

Listed:
  • Juan Carlos Yam-Puc

    (University of Cambridge)

  • Zhaleh Hosseini

    (University of Cambridge)

  • Emily C. Horner

    (University of Cambridge)

  • Pehuén Pereyra Gerber

    (University of Cambridge
    University of Cambridge)

  • Nonantzin Beristain-Covarrubias

    (University of Cambridge)

  • Robert Hughes

    (University of Cambridge)

  • Aleksei Lulla

    (University of Cambridge)

  • Maria Rust

    (University of Cambridge)

  • Rebecca Boston

    (University of Cambridge)

  • Magda Ali

    (University of Cambridge)

  • Katrin Fischer

    (University of Cambridge)

  • Edward Simmons-Rosello

    (University of Cambridge)

  • Martin O’Reilly

    (University of Cambridge)

  • Harry Robson

    (University of Cambridge)

  • Lucy H. Booth

    (University of Cambridge)

  • Lakmini Kahanawita

    (University of Cambridge)

  • Andrea Correa-Noguera

    (Cambridge University NHS Hospitals Foundation Trust)

  • David Favara

    (Cambridge University NHS Hospitals Foundation Trust)

  • Lourdes Ceron-Gutierrez

    (Cambridge University NHS Hospitals Foundation Trust)

  • Baerbel Keller

    (University of Freiburg
    University of Freiburg)

  • Andrew Craxton

    (University of Cambridge)

  • Georgina S. F. Anderson

    (University of Cambridge)

  • Xiao-Ming Sun

    (University of Cambridge)

  • Anne Elmer

    (NIHR Cambridge Clinical Research Facility)

  • Caroline Saunders

    (NIHR Cambridge Clinical Research Facility)

  • Areti Bermperi

    (NIHR Cambridge Clinical Research Facility)

  • Sherly Jose

    (NIHR Cambridge Clinical Research Facility)

  • Nathalie Kingston

    (Cambridge University Hospitals NHS Foundation Trust)

  • Thomas E. Mulroney

    (University of Cambridge)

  • Lucia P. G. Piñon

    (University of Cambridge)

  • Michael A. Chapman

    (University of Cambridge)

  • Sofia Grigoriadou

    (Barts Health)

  • Marion MacFarlane

    (University of Cambridge)

  • Anne E. Willis

    (University of Cambridge)

  • Kiran R. Patil

    (University of Cambridge)

  • Sarah Spencer

    (University of Cambridge)

  • Emily Staples

    (University of Cambridge
    Cambridge University NHS Hospitals Foundation Trust)

  • Klaus Warnatz

    (University of Freiburg
    University of Freiburg
    University Hospital Zurich)

  • Matthew S. Buckland

    (Barts Health
    Section of Cellular and Molecular Immunology)

  • Florian Hollfelder

    (University of Cambridge)

  • Marko Hyvönen

    (University of Cambridge)

  • Rainer Döffinger

    (Cambridge University NHS Hospitals Foundation Trust)

  • Christine Parkinson

    (Cambridge University NHS Hospitals Foundation Trust)

  • Sara Lear

    (Cambridge University NHS Hospitals Foundation Trust)

  • Nicholas J. Matheson

    (University of Cambridge
    University of Cambridge
    NHS Blood and Transplant)

  • James E. D. Thaventhiran

    (University of Cambridge
    Cambridge University NHS Hospitals Foundation Trust)

Abstract

Age-associated B cells (ABC) accumulate with age and in individuals with different immunological disorders, including cancer patients treated with immune checkpoint blockade and those with inborn errors of immunity. Here, we investigate whether ABCs from different conditions are similar and how they impact the longitudinal level of the COVID-19 vaccine response. Single-cell RNA sequencing indicates that ABCs with distinct aetiologies have common transcriptional profiles and can be categorised according to their expression of immune genes, such as the autoimmune regulator (AIRE). Furthermore, higher baseline ABC frequency correlates with decreased levels of antigen-specific memory B cells and reduced neutralising capacity against SARS-CoV-2. ABCs express high levels of the inhibitory FcγRIIB receptor and are distinctive in their ability to bind immune complexes, which could contribute to diminish vaccine responses either directly, or indirectly via enhanced clearance of immune complexed-antigen. Expansion of ABCs may, therefore, serve as a biomarker identifying individuals at risk of suboptimal responses to vaccination.

Suggested Citation

  • Juan Carlos Yam-Puc & Zhaleh Hosseini & Emily C. Horner & Pehuén Pereyra Gerber & Nonantzin Beristain-Covarrubias & Robert Hughes & Aleksei Lulla & Maria Rust & Rebecca Boston & Magda Ali & Katrin Fis, 2023. "Age-associated B cells predict impaired humoral immunity after COVID-19 vaccination in patients receiving immune checkpoint blockade," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-38810-0
    DOI: 10.1038/s41467-023-38810-0
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    References listed on IDEAS

    as
    1. Dami A. Collier & Isabella A. T. M. Ferreira & Prasanti Kotagiri & Rawlings P. Datir & Eleanor Y. Lim & Emma Touizer & Bo Meng & Adam Abdullahi & Anne Elmer & Nathalie Kingston & Barbara Graves & Emma, 2021. "Age-related immune response heterogeneity to SARS-CoV-2 vaccine BNT162b2," Nature, Nature, vol. 596(7872), pages 417-422, August.
    2. Matthew S. Buckland & James B. Galloway & Caoimhe Nic Fhogartaigh & Luke Meredith & Nicholas M. Provine & Stuart Bloor & Ane Ogbe & Wioleta M. Zelek & Anna Smielewska & Anna Yakovleva & Tiffeney Mann , 2020. "Treatment of COVID-19 with remdesivir in the absence of humoral immunity: a case report," Nature Communications, Nature, vol. 11(1), pages 1-11, December.
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