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

26 Pages Posted: 12 Oct 2021

See all articles by Helen Marie Parry

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 - Centre for Virus Research (CVR)

Chris Davis

University of Glasgow

Brian Willett

University of Glasgow - Centre for Virus Research (CVR)

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 - Institute of Immunology and Immunotherapy

Dawn Brant

University of Birmingham

Ashley Otter

UK Health Security Agency

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

More...

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 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.

Funding Information: This work was partially supported by the UK Coronavirus Immunology Consortium (UK-CIC) funded by DHSC/UKRI and the National Core Studies Immunity programme.

Declaration of Interests: The authors declare no conflicts of interest.

Ethics Approval Statement: Informed consent was obtained by remote consultation and work performed under the CIA UPH IRAS approval (REC 20\NW\0240) from North-West and Preston ethics committee and conducted according to the Declaration of Helsinki.

Keywords: CLL, COVID-19, SARS-CoV-2, Vaccination

Suggested Citation

Parry, Helen Marie and McIlroy, Graham and Bruton, Rachel and Damery, Sarah and Tyson, Grace and Logan, Nicola and Davis, Chris and Willett, Brian and Zuo, Jianmin and Ali, Myah and Kaur, Manjit and Stephens, Christine and Brant, Dawn and Otter, Ashley and McSkeane, Tina and Rolfe, Hayley and Faustini, Sian and Richter, Alex G. and Lee, Sophie and Wandroo, Farooq and Shafeek, Salim and Pratt, Guy and Paneesha, Shankara and Moss, Paul, Impaired Neutralisation of SARS-CoV-2 Delta Variant in Vaccinated Patients With B Cell Chronic Lymphocytic Leukaemia. Available at SSRN: https://ssrn.com/abstract=3941045 or http://dx.doi.org/10.2139/ssrn.3941045

Helen Marie Parry

University of Birmingham - Institute of Immunology and Immunotherapy ( email )

Birmingham
United Kingdom

Graham McIlroy

University of Birmingham - Institute of Cancer and Genomic Sciences ( email )

Birmingham
United Kingdom

Rachel Bruton

University of Birmingham - Institute of Immunology and Immunotherapy ( email )

Birmingham
United Kingdom

Sarah Damery

University of Birmingham ( email )

Edgbaston, Birmingham B15 2TT
United Kingdom

Grace Tyson

University of Glasgow ( email )

Adam Smith Business School
Glasgow, G12 8LE
United Kingdom

Nicola Logan

University of Glasgow - Centre for Virus Research (CVR) ( email )

Chris Davis

University of Glasgow ( email )

Adam Smith Business School
Glasgow, G12 8LE
United Kingdom

Brian Willett

University of Glasgow - Centre for Virus Research (CVR) ( email )

Jianmin Zuo

University of Birmingham - Institute of Immunology and Immunotherapy ( email )

Birmingham
United Kingdom

Myah Ali

University of Birmingham - Institute of Immunology and Immunotherapy ( email )

Birmingham
United Kingdom

Manjit Kaur

University of Birmingham ( email )

Edgbaston, Birmingham B15 2TT
United Kingdom

Christine Stephens

University of Birmingham - Institute of Immunology and Immunotherapy ( email )

Dawn Brant

University of Birmingham ( email )

Edgbaston, B15 2TT
United Kingdom

Ashley Otter

UK Health Security Agency ( email )

London
United Kingdom

Tina McSkeane

University of Birmingham - Cancer Research UK Clinical Trials Unit ( email )

Birmingham
United Kingdom

Hayley Rolfe

University of Birmingham - Cancer Research UK Clinical Trials Unit ( email )

Birmingham
United Kingdom

Sian Faustini

University of Birmingham - Institute of Cancer and Genomic Sciences

Birmingham
United Kingdom

University of Birmingham - Clinical Immunology Service ( email )

United Kingdom

Alex G. Richter

University of Birmingham - Institute of Cancer and Genomic Sciences ( email )

Edgbaston
Birminham, Birmingham B152TT
United Kingdom

University of Birmingham - Clinical Immunology Service ( email )

Birmingham
United Kingdom

Sophie Lee

Government of the United Kingdom - Royal Wolverhampton NHS Trust ( email )

Wolverhampton
United Kingdom

Farooq Wandroo

Barking, Havering and Redbridge University Hospitals NHS Trust - Sandwell and West Birmingham Hospitals NHS Trust ( email )

Birmingham
United Kingdom

Salim Shafeek

Herefordshire and Worcestershire Health and Care NHS Trust ( email )

Worcester
United Kingdom

Guy Pratt

Government of the United Kingdom - University Hospitals Birmingham ( email )

United Kingdom

Shankara Paneesha

University Hospitals Birmingham - Birmingham Heartlands Hospital ( email )

United Kingdom

Paul Moss (Contact Author)

University of Birmingham - Institute of Immunology and Immunotherapy ( email )

Birmingham
United Kingdom

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