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

Annika Fendler; Scott T C Shepherd; Lewis Au; Mary Wu; Ruth Harvey; Katalin A Wilkinson; Andreas M Schmitt; Zayd Tippu; Benjamin Shum; Sheima Farag; Aljosja Rogiers; Eleanor Carlyle; Kim Edmonds; Lyra Del Rosario; Karla Lingard; Mary Mangwende; Lucy Holt; Hamid Ahmod; Justine Korteweg; Tara Foley; Taja Barber; Andrea Emslie-Henry; Niamh Caulfield-Lynch; Fiona Byrne; Daqi Deng; Svend Kjaer; Ok-Ryul Song; Christophe J Queval; Caitlin Kavanagh; Emma C Wall; Edward J Carr; Simon Caidan; Mike Gavrielides; James I MacRae; Gavin Kelly; Kema Peat; Denise Kelly; Aida Murra; Kayleigh Kelly; Molly O'Flaherty; Robyn L Shea; Gail Gardner; Darren Murray; Sanjay Popat; Nadia Yousaf; Shaman Jhanji; Kate Tatham; David Cunningham; Nicholas Van As; Kate Young; Andrew J S Furness; Lisa Pickering; Rupert Beale; Charles Swanton; Sonia Gandhi; Steve Gamblin; David L V Bauer; George Kassiotis; Michael Howell; Emma Nicholson; Susanna Walker; Robert J Wilkinson; James Larkin; Samra Turajlic

doi:10.1016/j.xcrm.2022.100781

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

Cell Rep Med. 2022 Oct 18;3(10):100781. doi: 10.1016/j.xcrm.2022.100781. Epub 2022 Sep 27.

Authors

Annika Fendler¹, Scott T C Shepherd², Lewis Au², Mary Wu³, Ruth Harvey⁴, Katalin A Wilkinson⁵, Andreas M Schmitt⁶, Zayd Tippu², Benjamin Shum², Sheima Farag⁶, Aljosja Rogiers⁶, Eleanor Carlyle⁶, Kim Edmonds⁶, Lyra Del Rosario⁶, Karla Lingard⁶, Mary Mangwende⁶, Lucy Holt⁶, Hamid Ahmod⁶, Justine Korteweg⁶, Tara Foley⁶, Taja Barber¹, Andrea Emslie-Henry¹, Niamh Caulfield-Lynch¹, Fiona Byrne¹, Daqi Deng¹, Svend Kjaer⁷, Ok-Ryul Song⁸, Christophe J Queval⁸, Caitlin Kavanagh³, Emma C Wall⁹, Edward J Carr¹⁰, Simon Caidan¹¹, Mike Gavrielides¹², James I MacRae¹³, Gavin Kelly¹⁴, Kema Peat⁶, Denise Kelly⁶, Aida Murra⁶, Kayleigh Kelly⁶, Molly O'Flaherty⁶, Robyn L Shea¹⁵, Gail Gardner¹⁶, Darren Murray¹⁶, Sanjay Popat¹⁷, Nadia Yousaf¹⁸, Shaman Jhanji¹⁹, Kate Tatham¹⁹, David Cunningham²⁰, Nicholas Van As²¹, Kate Young⁶, Andrew J S Furness⁶, Lisa Pickering⁶, Rupert Beale²², Charles Swanton²³, Sonia Gandhi²⁴, Steve Gamblin²⁵, David L V Bauer²⁶, George Kassiotis²⁷, Michael Howell⁸, Emma Nicholson²⁸, Susanna Walker¹⁹, Robert J Wilkinson²⁹, James Larkin³⁰, Samra Turajlic³¹

Affiliations

¹ Cancer Dynamics Laboratory, The Francis Crick Institute, London NW1 1AT, UK.
² Cancer Dynamics Laboratory, The Francis Crick Institute, London NW1 1AT, UK; 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; Wellcome Center for Infectious Disease Research in Africa, University of Cape Town, Observatory 7925, Republic of South Africa.
⁶ Skin and Renal Units, The Royal Marsden NHS Foundation Trust, London SW3 6JJ, UK.
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 High Throughput Screening Laboratory, The Francis Crick Institute, London NW1 1AT, UK; 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; Translational Cancer Biochemistry Laboratory, The Institute of Cancer Research, London SW7 3RP, UK.
¹⁶ Department of Pathology, The Royal Marsden NHS Foundation Trust, London NW1 1AT, UK.
¹⁷ Lung Unit, The Royal Marsden NHS Foundation Trust, London SW3 6JJ, UK.
¹⁸ Lung Unit, The Royal Marsden NHS Foundation Trust, London SW3 6JJ, UK; 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 Clincal Oncology Unit, The Royal Marsden NHS Foundation Trust, London NW1 1AT, UK.
²² Cell Biology of Infection Laboratory, The Francis Crick Institute, London NW1 1AT, UK; 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; University College London Cancer Institute, London WC1E 6DD, UK.
²⁴ Neurodegeneration Biology Laboratory, The Francis Crick Institute, London NW1 1AT, UK; UCL Queen Square Institute of Neurology, Queen Square, London WC1N 3BG, UK.
²⁵ Structural Biology of Disease Processes Laboratory, The Francis Crick Institute, London NW1 1AT, UK.
²⁶ RNA Virus Replication Laboratory, The Francis Crick Institute, London NW1 1AT, UK.
²⁷ Retroviral Immunology Laboratory, The Francis Crick Institute, London NW1 1AT, UK.
²⁸ Haemato-oncology Unit, The Royal Marsden NHS Foundation Trust, London SW3 6JJ, UK; Haemato-oncology Unit, The Institute of Cancer Research, London SW7 3RP, UK.
²⁹ Tuberculosis Laboratory, The Francis Crick Institute, London NW1 1AT, UK; Wellcome Center for Infectious Disease Research in Africa, University of Cape Town, Observatory 7925, Republic of South Africa; Department of Infectious Disease, Imperial College London, London W2 0NN, UK.
³⁰ Skin and Renal Units, The Royal Marsden NHS Foundation Trust, London SW3 6JJ, UK; Melanoma and Kidney Cancer Team, The Institute of Cancer Research, London SW7 3RP, UK.
³¹ Cancer Dynamics Laboratory, The Francis Crick Institute, London NW1 1AT, UK; Skin and Renal Units, The Royal Marsden NHS Foundation Trust, London SW3 6JJ, UK; Melanoma and Kidney Cancer Team, The Institute of Cancer Research, London SW7 3RP, UK. Electronic address: samra.turajlic@crick.ac.uk.

Abstract

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.

Keywords: COVID-19; SARS-CoV-2; T cells; blood cancer; neutralizing antibodies; variants of concern.

Publication types

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

MeSH terms

Antibodies, Neutralizing
Antibodies, Viral
BNT162 Vaccine
COVID-19 Vaccines* / immunology
COVID-19* / prevention & control
Clinical Studies as Topic
Humans
Immunity
Neoplasms*
SARS-CoV-2

Substances

Antibodies, Neutralizing
Antibodies, Viral
BNT162 Vaccine
COVID-19 Vaccines

Supplementary concepts

SARS-CoV-2 variants

Associated data