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

This research has not been peer-reviewed. It is a preliminary report that should not be regarded as conclusive, guide clinical practice or health-related behaviour, or be reported in news media as established information.

The effect of immune checkpoint blockade on COVID-19 immunity is unclear. In this study, we determine whether immune checkpoint blockade expanded age-associated B cells (ABCs) are similar to those present in other conditions, and whether they enhance or detract from the COVID-19 vaccine responses. First, we use single cell RNA sequencing (scRNAseq) to show that ABCs arising from distinct aetiologies have common transcriptional profiles and may be further subdivided according to expression of genes associated with different immune functions, including the autoimmune regulator (AIRE). Next, we perform detailed longitudinal profiling of the COVID-19 vaccination response in patients. Finally, we show that high pre-vaccination ABC frequency correlates with decreased levels of antigen-specific memory B cells, and reduced magnitude and longevity of neutralising capacity against authentic SARS-CoV-2 virus. Expansion of ABCs is a biomarker for individuals with cancer requiring additional or more frequent booster immunisation against COVID-19.


Author list



  1. Medical Research Council Toxicology Unit, School of Biological Sciences, University of Cambridge, Cambridge, UK.
  2. Cambridge Institute of Therapeutic Immunology and Infectious Disease (CITIID), University of Cambridge, UK
  3. Department of Medicine, University of Cambridge, Cambridge, UK
  4. Department of Clinical Immunology, Barts Health, London, UK.
  5. UCL GOSH Institute of Child Health Division of Infection and Immunity, Section of Cellular and Molecular Immunology, London, UK.
  6. Department of Biochemistry, University of Cambridge, Cambridge, UK
  7. NIHR Cambridge Clinical Research Facility
  8. Cambridge University NHS Hospitals Foundation Trust, Cambridge, UK
  9. NHS Blood and Transplant, Cambridge, UK


Juan Carlos Yam-Puc1†*, Zhaleh Hosseini1†, Emily C. Horner1†, Pehuén Pereyra Gerber2,3†, Nonantzin Beristain-Covarrubias1†, Robert Hughes1†, Maria Rust1, Rebecca H. Boston1, Magda Ali1, Edward Simmons-Rosello1, Martin O’Reilly1, Harry Robson1, Lucy H. Booth1, Lakmini Kahanawita1, Sofia Grigoriadou4, Andrea Correa-Noguera5, Lourdes Ceron-Gutierrez5, Thomas Mulroney1, Aleksei Lulla6, Katrin Fischer6, Andrew Craxton1, Georgina S.F. Anderson1, Xiao-Ming Sun1, Anne Elmer7, Caroline Saunders7, Areti Bermperi7, Sherly Jose7, Mike Chapman1, Marion MacFarlane1, Anne E. Willis1, Kiran R. Patil1, Florian Hollfelder6, Marko Hyvönen6, CITIID-NIHR COVID-19 BioResource Collaboration, Sarah Spencer1, Emily Staples1, Matthew S. Buckland4,5, Rainer Döffinger8, Christine Parkinson8§, Sara Lear8§, Nicholas J. Matheson2,3,,8,9§, James E. D. Thaventhiran1,2,8§*.

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