Antibody Responses After First and Second COVID-19 Vaccination in Patients With Chronic Lymphocytic Leukaemia


Preprints with The Lancet

Contributing to research themes:

This research has not been peer-reviewed. This is a preliminary report that should not be regarded as conclusive, guide clinical practice/health-related behaviour, or be reported in news media as established information.


Background: B cell chronic lymphocytic leukaemia (CLL) is associated with immune suppression and patients are at increased clinical risk following SARS-CoV-2 infection. Covid-19 vaccines offer the potential for protection against severe infection but relatively little is known regarding the profile of the antibody response following first or second vaccination.

Methods: We studied spike-specific antibody responses following first and/or second Covid-19 vaccination in 299 patients with CLL compared with healthy donors. 13 patients underwent a standard interval (3-week) vaccine regimen whilst 286 underwent extended interval (10-12 week) vaccination. 154 patients received the BNT162b2 mRNA vaccine and 145 patients received ChAdOx1. Blood samples were taken either by venepuncture or as dried blood spots on filter paper. 267 samples were taken at 5 weeks after the first vaccine for patients on the extended interval regimen and 13 and 42 samples were taken at 2-4 weeks after the second vaccine in patients on the standard or extended vaccine regimens respectively.

Findings: Spike-specific antibody responses were detectable in 34% of patients with CLL after one vaccine compared to 94% in healthy donors with antibody titres 104-fold lower in the patient group. Antibody responses increased to 75% after second vaccine, compared to 100% in healthy donors, although titres remained lower. Multivariate analysis showed that current treatment with BTK inhibitors or IgA deficiency were independently associated with failure to generate an antibody response after the second vaccine.

Interpretation: Antibody responses after both the first and second Covid-19 vaccine are lower in patients with CLL compared to age-matched donors. This is particularly marked in patients who are taking BTK inhibitors or have serum IgA deficiency. Further approaches such as repeat vaccination or administration of prophylactic antibody may be worthy of investigation for some patients.

Author list:

Author Affiliations:

1) Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham. B15 2TT, UK

2) Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham B15 2TT, UK

3) Institute of Applied Health Research, University of Birmingham, Birmingham, B15 2TT, UK

4) National infection Service, Public Health England, Porton Down, Salisbury, SP4 OJG, UK

5) Cancer Research UK Clinical Trials Unit, University of Birmingham, B15 2TT

6) St. James’s University Hospital, Leeds Teaching Hospitals NHS Trust, Leeds LS9 7TF.

7) Queen Elizabeth Hospital, University Hospitals Birmingham, Birmingham B15 2TH

8) Birmingham Heartlands Hospital, University Hospitals Birmingham, Bordesley Green East. B9 5SS


Helen Marie Parry1, Graham McIlroy2, Rachel Bruton1, Myah Ali1, Christine Stephens1, S. Damery3, Ashley Otter4, Tina McSkeane5, Hayley Rolfe5, Sian Faustini1, Nadezhda Wall1, P. Hillmen6, Guy Pratt7, Shankara Paneesha8, Jianmin Zuo1, Alex G. Richter1, Paul Moss1,7