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

  1. Sean H. Lim
  2. Beth Stuart
  3. Debora Joseph-Pietras
  4. Marina Johnson
  5. Nicola Campbell
  6. Adam Kelly
  7. Danielle Jeffrey
  8. Anna H. Turaj
  9. Kate Rolfvondenbaumen
  10. Celine Galloway
  11. Thomas Wynn
  12. Adam R. Coleman
  13. Benjamin Ward
  14. Karen Long
  15. Helen Coleman
  16. Carina Mundy
  17. Andrew T. Bates
  18. Diana Ayres
  19. Robert Lown
  20. Janlyn Falconer
  21. Oliver Brake
  22. James Batchelor
  23. Victoria Willimott
  24. Anna Bowzyk Al-Naeeb
  25. Lisa Robinson
  26. Ann O’Callaghan
  27. Graham P. Collins
  28. Tobias Menne
  29. Saul N. Faust
  30. Christopher P. Fox
  31. Matthew Ahearne
  32. Peter W. M. Johnson
  33. Andrew J. Davies
  34. David Goldblatt

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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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  1. Version published to 10.1038/s43018-022-00364-3
  2. ScreenIT

    SciScore for 10.1101/2021.12.08.21266760: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    EthicsConsent: It is a multicentre, prospective observational cohort study which enrolled participants from local hospital databases or outpatient clinics from January to September 2021, after informed consent.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Participants with nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) were classified as indolent B-NHL for the purpose of this study due to the treatment of this disease with anti-CD20 monoclonal antibodies.
    anti-CD20
    suggested: None
    Pseudoneutralization (ACE2 receptor blocking) assay: Samples with detectable anti-S and anti-RBD IgG antibodies were evaluated by a pseudoneutralization assay as previously described in the WHO International Reference Laboratory for Pneumococcal Serology at University College London, London, UK (Johnson et al., 2020).
    anti-S
    suggested: None
    anti-RBD IgG
    suggested: None
    Briefly, ELISpot plates were coated with anti-human IFNγ antibody overnight.
    anti-human IFNγ
    suggested: None
    Software and Algorithms
    SentencesResources
    Data was analysed using Cytobank (Cytobank).
    Cytobank
    suggested: (Cytobank, RRID:SCR_014043)
    All analyses were done in Stata, version 16.0 and GraphPad Prism, version 9.
    GraphPad Prism
    suggested: (GraphPad Prism, RRID:SCR_002798)

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    However, the caveat being that this population largely comprised of patients with HL who tend to be younger than those with B-NHL. The majority of participants with other tumours types treated with chemotherapy also tend to mount antibody responses to the vaccine (Greenberger et al., 2021b; Waldhorn et al., 2021). Data on cellular responses post SARS-CoV-2 vaccination are limited and where reported, most cohorts tend to be relatively small or heterogeneous in disease type, with the exception of Ehmsen and colleagues who analysed 323 participants, mostly comprising chronic lymphocytic leukaemia and multiple myeloma (Ehmsen et al., 2021; Fendler et al., 2021; McKenzie et al., 2021). There is an increasing body of data demonstrating that T cells can protect individuals with impaired antibody responses to COVID-19, or post-vaccination, against severe infection(Apostolidis et al., 2021; Bange et al., 2021). Consistent with other studies, we detected T-cell responses in participants on anti-CD20(Fendler et al., 2021). Due to the size of our dataset, we were also able to ascertain that systemic therapy had minimal effect on T-cell responses. One significant finding is the observation of anti-S T-cell responses in patients with HL regardless of treatment. It has long been suggested that these patients have a defect in their cellular immunity but our data shows no evidence of excess functional T-cell impairment when compared to B-NHL. (Foukaneli et al., 2020; Poppema, 1996) Reduced T-...

    Results from TrialIdentifier: We found the following clinical trial numbers in your paper:

    IdentifierStatusTitle
    NCT4858568Trial number did not resolve on clinicaltrials.gov. Is the number correct?NA

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    Results from scite Reference Check: We found no unreliable references.

    About SciScore

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

  3. Version published to 10.1101/2021.12.08.21266760v1 on medRxiv