Helen Parry1, Graham McIlroy2, Rachel Bruton1, Sarah Damery3, Grace Tyson4, Nicola Logan, Chris Davis4, Brian Willett4, Jianmin Zuo1, Myah Ali1, Manjit Kaur1, Christine Stephens1, Dawn Brant1, Ashley Otter5, Tina McSkeane6, Hayley Rolfe6, Sian Faustini1, Alex Richter1, Sophie Lee7, Farooq Wandroo8, Salim Shafeek9, Guy Pratt10, Shankara Paneesha11, Paul Moss12. 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. MRC- University of Glasgow Centre for Virus Research, University of Glasgow, Glasgow, G61 1QH, UK. 5. UK Health Security Agency, Porton Down, Salisbury, SP4 OJG, UK. 6. Cancer Research UK Clinical Trials Unit, University of Birmingham, Birmingham, B15 2TT, UK. 7. Department of Haematology, The Royal Wolverhampton NHS Trust. Wolverhampton Hospital, Wolverhampton, WV10 0QP, UK. 8. Department of Haematology. Sandwell and West Birmingham, NHS Trust, Birmingham, B18 7QH, UK. 9. Department of Haematology, Worcestershire Acute Hospitals NHS Trust, Worcester, WR5 1DD, UK. 10. Queen Elizabeth Hospital, University Hospitals Birmingham, Birmingham, B15 2TH, UK. 11. Birmingham Heartlands Hospital, University Hospitals Birmingham, Birmingham, B9 5SS, UK. 12. Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, B15 2TT, UK. p.moss@bham.ac.uk.
Abstract
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.
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.
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