Functional immune responses against SARS-CoV-2 variants of concern after fourth COVID-19 vaccine dose or infection in patients with blood cancer

Patients with blood cancer continue to have a greater risk of inadequate immune responses following three COVID-19 vaccine doses and risk of severe COVID-19 disease. In the context of the CAPTURE study (NCT03226886), we report immune responses in 80 patients with blood cancer who received a fourth dose of BNT162b2. We measured neutralizing antibody titers (NAbTs) using a live virus microneutralization assay against wild-type (WT), Delta, and Omicron BA.1 and BA.2 and T cell responses against WT and Omicron BA.1 using an activation-induced marker (AIM) assay. The proportion of patients with detectable NAb titers and T cell responses after the fourth vaccine dose increased compared with that after the third vaccine dose. Patients who received B cell-depleting therapies within the 12 months before vaccination have the greatest risk of not having detectable NAbT. In addition, we report immune responses in 57 patients with breakthrough infections after vaccination.

Author list

 

Affiliations:

  1. Cancer Dynamics Laboratory, The Francis Crick Institute, London NW1 1AT, UK
  2. Skin and Renal Units, The Royal Marsden NHS Foundation Trust, London SW3 6JJ, UK
  3. COVID Surveillance Unit, The Francis Crick Institute, London NW1 1AT, UK
  4. Worldwide Influenza Centre, The Francis Crick Institute, London NW1 1AT, UK
  5. Tuberculosis Laboratory, The Francis Crick Institute, London NW1 1AT, UK
  6. Wellcome Center for Infectious Disease Research in Africa, University of Cape Town, Observatory 7925, Republic of South Africa
  7. Structural Biology Scientific Technology Platform, The Francis Crick Institute, London NW1 1AT, UK
  8. High Throughput Screening Laboratory, The Francis Crick Institute, London NW1 1AT, UK
  9. University College London Hospitals NHS Foundation Trust Biomedical Research Centre, London WC1E 6BT, UK
  10. Cell Biology of Infection Laboratory, The Francis Crick Institute, London NW1 1AT, UK
  11. Safety, Health & Sustainability, The Francis Crick Institute, London NW1 1AT, UK
  12. Scientific Computing Scientific Technology Platform, The Francis Crick Institute, London NW1 1AT, UK
  13. Metabolomics Scientific Technology Platform, The Francis Crick Institute, London NW1 1AT, UK
  14. Department of Bioinformatics and Biostatistics, The Francis Crick Institute, London, UK
  15. Department of Pathology, The Royal Marsden NHS Foundation Trust, London NW1 1AT, UK
  16. Translational Cancer Biochemistry Laboratory, The Institute of Cancer Research, London SW7 3RP, UK
  17. Lung Unit, The Royal Marsden NHS Foundation Trust, London SW3 6JJ, UK
  18. Acute Oncology Service, The Royal Marsden NHS Foundation Trust, London SW3 6JJ, UK
  19. Anaesthetics, Perioperative Medicine and Pain Department, The Royal Marsden NHS Foundation Trust, London SW3 6JJ, UK
  20. Gastrointestinal Unit, The Royal Marsden NHS Foundation Trust, Sutton SM2 5PT, UK
  21. Clinical Oncology Unit, The Royal Marsden NHS Foundation Trust, London NW1 1AT, UK
  22. Division of Medicine, University College London, London NW1 2PG, UK
  23. Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London NW1 1AT, UK
  24. University College London Cancer Institute, London WC1E 6DD, UK
  25. Neurodegeneration Biology Laboratory, The Francis Crick Institute, London NW1 1AT, UK
  26. UCL Queen Square Institute of Neurology, Queen Square, London WC1N 3BG, UK
  27. Structural Biology of Disease Processes Laboratory, The Francis Crick Institute, London NW1 1AT, UK
  28. RNA Virus Replication Laboratory, The Francis Crick Institute, London NW1 1AT, UK
  29. Retroviral Immunology Laboratory, The Francis Crick Institute, London NW1 1AT, UK
  30. Haemato-oncology Unit, The Royal Marsden NHS Foundation Trust, London SW3 6JJ, UK
  31. Haemato-oncology Unit, The Institute of Cancer Research, London SW7 3RP, UK
  32. Department of Infectious Disease, Imperial College London, London W2 0NN, UK
  33. Melanoma and Kidney Cancer Team, The Institute of Cancer Research, London SW7 3RP, UK

Authors:

Annika Fendler,1,34 Scott T.C. Shepherd,1,2,34 Lewis Au,1,2,34 Mary Wu,3,34 Ruth Harvey,4,34 Katalin A. Wilkinson,5,6,34 Andreas M. Schmitt,2 Zayd Tippu,1,2 Benjamin Shum,1,2 Sheima Farag,2 Aljosja Rogiers,2 Eleanor Carlyle,2
Kim Edmonds,2 Lyra Del Rosario,2 Karla Lingard,2 Mary Mangwende,2 Lucy Holt,2 Hamid Ahmod,2 Justine Korteweg,2 Tara Foley,2 Taja Barber,1 Andrea Emslie-Henry,1 Niamh Caulfield-Lynch,1 Fiona Byrne,1 Daqi Deng,1 Svend Kjaer,7 Ok-Ryul Song,8 Christophe J. Queval,8 Caitlin Kavanagh,3 Emma C. Wall,8,9 Edward J. Carr,10 Simon Caidan,11 Mike Gavrielides,12 James I. MacRae,13 Gavin Kelly,14 Kema Peat,2 Denise Kelly,2 Aida Murra,2 Kayleigh Kelly,2 Molly O’Flaherty,2 Robyn L. Shea,15,16 Gail Gardner,15 Darren Murray,15 Sanjay Popat,17 Nadia Yousaf,17,18 Shaman Jhanji,19 Kate Tatham,19 David Cunningham,20 Nicholas Van As,21 Kate Young,2 Andrew J.S. Furness,2 Lisa Pickering,2 Rupert Beale,10,22 Charles Swanton,23,24 Sonia Gandhi,25,26 Steve Gamblin,27 David L.V. Bauer,28 George Kassiotis,29 Michael Howell,8 Emma Nicholson,30,31 Susanna Walker,19 Robert J. Wilkinson,5,6,32 James Larkin,2,33 and Samra Turajlic1,2,33,35,*

 

Novel Coronavirus SARS-CoV-2

10.1016/j.xcrm.2022.100781

Cell Reports Medicine

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