. 2022 Oct 18;3(10):100781.

doi: 10.1016/j.xcrm.2022.100781. Epub 2022 Sep 27.

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

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.

PMID: 36240755
PMCID: PMC9513326
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

Annika Fendler et al. Cell Rep Med. 2022.

. 2022 Oct 18;3(10):100781.

doi: 10.1016/j.xcrm.2022.100781. Epub 2022 Sep 27.

Authors

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.

PMID: 36240755
PMCID: PMC9513326
DOI: 10.1016/j.xcrm.2022.100781

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.

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Conflict of interest statement

Declaration of interests The authors declare no competing interest.

Figures

**Figure 1**
NAb and T cell responses after a fourth vaccine dose and breakthrough infections (A) NAbTs against Omicron BA.1, WT, and Delta were measured after the fourth vaccine dose. NAbT below (IC₅₀ titer <40) or above the quantitative range (IC₅₀ titer >2,560) are indicated by horizontal lines. (B) NAbTs against Omicron BA.1, BA.2, WT, or Delta after four vaccine doses. (C and D) Levels of (C) CD4⁺CD137⁺OX40⁺ or (D) CD8⁺CD137⁺CD69⁺ T cells in patients stimulated with WT or Omicron BA.1 full-length spike peptide pools after three or four vaccine doses. (E) NAbTs against Omicron BA.1, BA.2, WT, and Delta before and after breakthrough infection. Infections after two or three vaccine doses are displayed separately. Timing of blood sampling in relation to vaccination and infection is color-coded. The regression line and 95% CI were fitted using LOESS regression. (F and G) Comparison of NAbTs against Omicron BA.1, BA.2, WT, and Delta before infection (but after last vaccine dose) and after infection in patients with breakthrough infection after (F) two and (G) three vaccine doses. Violin plots denote the density of data, point-range denotes the median and the 25^th and 75^th percentiles. Patients are indicated as individual data points, and samples from individual patients are connected. The proportions of patients with detectable titers are visualized with pie charts (dark blue denotes patients with IC₅₀ titers >40). Biological replicates are patient subjects. There were no technical replicates.

See this image and copyright information in PMC

References

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

Affiliations

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

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

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Supplementary concepts

Associated data

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