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Immune responses against SARS-CoV-2 variants after two and three doses of vaccine in B-cell malignancies: UK PROSECO study

Immune responses against SARS-CoV-2 variants after two and three doses of vaccine in B-cell malignancies: UK PROSECO study
Immune responses against SARS-CoV-2 variants after two and three doses of vaccine in B-cell malignancies: UK PROSECO study

Patients with hematological malignancies are at increased risk of severe COVID-19 outcomes due to compromised immune responses, but the insights of these studies have been compromised due to intrinsic limitations in study design. Here we present the PROSECO prospective observational study ( NCT04858568 ) on 457 patients with lymphoma that received two or three COVID-19 vaccine doses. We show undetectable humoral responses following two vaccine doses in 52% of patients undergoing active anticancer treatment. Moreover, 60% of patients on anti-CD20 therapy had undetectable antibodies following full vaccination within 12 months of receiving their anticancer therapy. However, 70% of individuals with indolent B-cell lymphoma displayed improved antibody responses following booster vaccination. Notably, 63% of all patients displayed antigen-specific T-cell responses, which increased after a third dose irrespective of their cancer treatment status. Our results emphasize the urgency of careful monitoring of COVID-19-specific immune responses to guide vaccination schemes in these vulnerable populations.

2662-1347
552-564
Lim, Sean H.
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Campbell, Nicola
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Lim, Sean H., Stuart, Beth, Joseph-Pietras, Debora, Johnson, Marina, Campbell, Nicola, Kelly, Adam, Jeffrey, Danielle, Turaj, Anna H, Rolfvondenbaumen, Kate, Galloway, Celine, Wynn, Thomas, Coleman, Adam R., Ward, Benjamin, Long, Karen, Coleman, Helen, Mundy, Carina, Bates, Andrew T., Ayres, Diana, Lown, Robert, Falconer, Janlyn, Brake, Oliver, Batchelor, James, Willimott, Victoria, Bowzyk Al-Naeeb, Anna, Robinson, Lisa, O'Callaghan, Ann, Collins, Graham P, Menne, Tobias, Faust, Saul N, Fox, Christopher P, Ahearne, Matthew, Johnson, Peter W M, Davies, Andrew J and Goldblatt, David (2022) Immune responses against SARS-CoV-2 variants after two and three doses of vaccine in B-cell malignancies: UK PROSECO study. Nature cancer, 3 (5), 552-564. (doi:10.1038/s43018-022-00364-3).

Record type: Article

Abstract

Patients with hematological malignancies are at increased risk of severe COVID-19 outcomes due to compromised immune responses, but the insights of these studies have been compromised due to intrinsic limitations in study design. Here we present the PROSECO prospective observational study ( NCT04858568 ) on 457 patients with lymphoma that received two or three COVID-19 vaccine doses. We show undetectable humoral responses following two vaccine doses in 52% of patients undergoing active anticancer treatment. Moreover, 60% of patients on anti-CD20 therapy had undetectable antibodies following full vaccination within 12 months of receiving their anticancer therapy. However, 70% of individuals with indolent B-cell lymphoma displayed improved antibody responses following booster vaccination. Notably, 63% of all patients displayed antigen-specific T-cell responses, which increased after a third dose irrespective of their cancer treatment status. Our results emphasize the urgency of careful monitoring of COVID-19-specific immune responses to guide vaccination schemes in these vulnerable populations.

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s43018-022-00364-3
Available under License Creative Commons Attribution.
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Accepted/In Press date: 10 March 2022
e-pub ahead of print date: 24 March 2022
Published date: May 2022
Additional Information: Funding Information: S.H.L., N.C., M.J., D.J.P., A.O., H.C., C.M., A.K., A.R.C., A.H.T., K.L., D.J., B.W., T.W., A.T.B., K.R., B.S., C.G., D.A., J.F., O.B., J.B., V.M., A.B.A.-N., L.R., T.M., P.W.M.J. and D.G. declare no competing interests. C.F. receives consultancy fees from AstraZeneca and participates in an advisory board for AstraZeneca. M.A. receives research funding from Pfizer. G.P.C. receives research funding from Pfizer and participates in advisory boards for AstraZeneca and Pfizer. R.L. reports receiving speaker fees and honoraria from Janssen. A.J.D. reports receiving research funding and honoraria from AstraZeneca and Janssen. S.N.F. participates in advisory boards related to vaccines or grants for contract commercial clinical trials that were paid to S.N.F.’s institution (with no personal payment of any kind) from AstraZeneca/Medimmune, Sanofi, Pfizer, Seqirus, Merck, GSK, J&J, Merck and Valneva, outside the submitted work. Funding Information: The PROSECO study is funded by the Blood Cancer UK Vaccine Research Collaborative, which is led by Blood Cancer UK in partnership with Myeloma UK, Anthony Nolan and the British Society for Haematology (21009) to S.H.L. and supported by Cancer Research UK Advanced Clinician Scientist Fellowship to S.H.L. (A27179), the Cancer Research UK/National Institute for Health Research (NIHR) Southampton Experimental Cancer Medicine Center to A.J.D. (A25141), the NIHR Southampton Clinical Research Facility (Southampton Research Biorepository) and NIHR Southampton Biomedical Research Center. D.G. receives support from the NIHR Great Ormond Street Biomedical Research Center. G.P.C. acknowledges support from the NIHR Oxford Biomedical Research Center and CRUK Experimental Cancer Medicines Center. We thank members of the Blood Cancer UK Vaccine Task Force for their advice. We thank J. Wilbur at Meso Scale Discovery for technical support and provision of laboratory reagents. We sincerely thank all the participating sites’ research staff for their hard work and we also thank the research participants. Publisher Copyright: © 2022, The Author(s). Copyright: Copyright 2022 Elsevier B.V., All rights reserved.

Identifiers

Local EPrints ID: 456562
URI: http://eprints.soton.ac.uk/id/eprint/456562
ISSN: 2662-1347
PURE UUID: fe7e9f0f-6bb5-4e9b-9348-db909e038e0f
ORCID for Beth Stuart: ORCID iD orcid.org/0000-0001-5432-7437
ORCID for James Batchelor: ORCID iD orcid.org/0000-0002-5307-552X
ORCID for Saul N Faust: ORCID iD orcid.org/0000-0003-3410-7642
ORCID for Peter W M Johnson: ORCID iD orcid.org/0000-0003-2306-4974
ORCID for Andrew J Davies: ORCID iD orcid.org/0000-0002-7517-6938

Catalogue record

Date deposited: 05 May 2022 16:33
Last modified: 18 Jun 2022 01:39

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Contributors

Author: Sean H. Lim
Author: Beth Stuart ORCID iD
Author: Debora Joseph-Pietras
Author: Marina Johnson
Author: Nicola Campbell
Author: Adam Kelly
Author: Danielle Jeffrey
Author: Anna H Turaj
Author: Kate Rolfvondenbaumen
Author: Celine Galloway
Author: Thomas Wynn
Author: Adam R. Coleman
Author: Benjamin Ward
Author: Karen Long
Author: Helen Coleman
Author: Carina Mundy
Author: Andrew T. Bates
Author: Diana Ayres
Author: Robert Lown
Author: Janlyn Falconer
Author: Oliver Brake
Author: James Batchelor ORCID iD
Author: Victoria Willimott
Author: Anna Bowzyk Al-Naeeb
Author: Lisa Robinson
Author: Ann O'Callaghan
Author: Graham P Collins
Author: Tobias Menne
Author: Saul N Faust ORCID iD
Author: Christopher P Fox
Author: Matthew Ahearne
Author: Andrew J Davies ORCID iD
Author: David Goldblatt

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