Impaired Neutralisation of SARS-CoV-2 Delta Variant in Vaccinated Patients With B Cell Chronic Lymphocytic Leukaemia

This research has not been peer-reviewed.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

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 2 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.

Interpretation: These findings demonstrate impaired antibody responses following dual COVID-19 vaccination in patients with CLL and further define patient risk groups. Furthermore, humoral 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.

Author list

 

Helen Marie Parry, University of Birmingham - Institute of Immunology and Immunotherapy

Graham McIlroy, University of Birmingham - Institute of Cancer and Genomic Sciences, 

Rachel Bruton, University of Birmingham - Institute of Immunology and Immunotherapy, 

Sarah Damery, University of Birmingham, 

Grace Tyson, University of Glasgow

Nicola Logan, University of Glasgow

Chris Davis, University of Glasgow

Brian Willett, University of Glasgow

Jianmin Zuo, University of Birmingham - Institute of Immunology and Immunotherapy

Myah Ali, University of Birmingham - Institute of Immunology and Immunotherapy

Manjit Kaur, University of Birmingham

Christine Stephens, University of Birmingham

Dawn Brant, University of Birmingham

Ashley Otter, Public Health England - National infection Service

Tina McSkeane, University of Birmingham - Cancer Research UK Clinical Trials Unit

Hayley Rolfe, University of Birmingham - Cancer Research UK Clinical Trials Unit

Sian Faustini, University of Birmingham - Institute of Cancer and Genomic Sciences; University of Birmingham - Clinical Immunology Service

Alex G. Richter, University of Birmingham - Institute of Cancer and Genomic Sciences; University of Birmingham - Clinical Immunology Service

Sophie Lee, Government of the United Kingdom - Royal Wolverhampton NHS Trust

Farooq Wandroo, Barking, Havering and Redbridge University Hospitals NHS Trust - Sandwell and West Birmingham Hospitals NHS Trust

Salim Shafeek, Herefordshire and Worcestershire Health and Care NHS Trust

Guy Pratt, Government of the United Kingdom - University Hospitals Birmingham

Shankara Paneesha, University Hospitals Birmingham - Birmingham Heartlands Hospital

Paul Moss, University of Birmingham - Institute of Immunology and Immunotherapy

Novel Coronavirus SARS-CoV-2

10.2139/ssrn.3941045

Preprints with the Lancet