Impaired neutralisation of SARS-CoV-2 delta variant in vaccinated patients with B cell chronic lymphocytic leukaemia

Helen Parry, Graham McIlroy, Paul Moss, Sarah Damery, Grace Tyson, Nicola Logan, Chris Davis, Brian Willett, Jianmin Zuo, Myah Ali, Manjit Kaur, Christine Stephens, Dawn Brant, Ashley Otter, Tina McSkeane, Hayley Rolfe, Sian Faustini, Alex Richter, Sophie Lee, Farooq WandrooSalim Shafeek, Guy Pratt, Shankara Paneesha, Paul Moss*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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BACKGROUND: Immune suppression is a clinical feature of chronic lymphocytic leukaemia (CLL), and patients show increased vulnerability to SARS-CoV-2 infection and suboptimal antibody responses.

METHOD: We studied antibody responses in 500 patients following dual COVID-19 vaccination to assess the magnitude, correlates of response, stability and functional activity of the spike-specific antibody response with two different vaccine platforms.

RESULTS: Spike-specific seroconversion post-vaccine was seen in 67% of patients compared to 100% of age-matched controls. Amongst responders, titres were 3.7 times lower than the control group. Antibody responses showed a 33% fall over the next 4 months. The use of an mRNA (n = 204) or adenovirus-based (n = 296) vaccine platform did not impact on antibody response. Male gender, BTKi therapy, prophylactic antibiotics use and low serum IgA/IgM were predictive of failure to respond. Antibody responses after CD20-targeted immunotherapy recovered 12 months post treatment. Post-vaccine sera from CLL patients with Spike-specific antibody response showed markedly reduced neutralisation of the SARS-CoV-2 delta variant compared to healthy controls. Patients with previous natural SARS-CoV-2 infection showed equivalent antibody levels and function as healthy donors after vaccination.

CONCLUSIONS: These findings demonstrate impaired antibody responses following dual COVID-19 vaccination in patients with CLL and further define patient risk groups. Furthermore, humoural protection against the globally dominant delta variant is markedly impaired in CLL patients and indicates the need for further optimisation of immune protection in this patient cohort.

Original languageEnglish
Article number3
Number of pages12
JournalJournal of Hematology and Oncology
Issue number1
Early online date9 Jan 2022
Publication statusPublished - Dec 2022

Bibliographical note

Funding Information:
This work was partially supported by National Core Studies Immunity and the UK Coronavirus Immunology Consortium (UK-CIC) funded by NIHR/UKRI. We thank Dr Rory Meade and the patients and staff at Harborne Medical Practice. We also thank Millie Manning, Danielle Sutherland, Tamsin Drury and Alex Bray for their help in recruitment.

This work was partially supported by the UK Coronavirus Immunology Consortium (UK-CIC) funded by DHSC/UKRI and the National Core Studies Immunity programme. Sponsors had no role in the study design, collection, analysis, interpretation of the data or write up of the report.

Publisher Copyright:
© 2021, The Author(s).


  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Neutralizing/immunology
  • Antibody Formation
  • COVID-19 Vaccines/immunology
  • COVID-19/complications
  • Female
  • HEK293 Cells
  • Humans
  • Leukemia, Lymphocytic, Chronic, B-Cell/complications
  • Male
  • Middle Aged
  • SARS-CoV-2/immunology
  • CLL
  • Antibody
  • Vaccination
  • Leukaemia
  • SARS-CoV-2

ASJC Scopus subject areas

  • Molecular Biology
  • Hematology
  • Oncology
  • Cancer Research


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