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 Wandroo; Salim Shafeek; Guy Pratt; Shankara Paneesha; Paul Moss

doi:10.1186/s13045-021-01219-7

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 journal › Article › peer-review

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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.

Original language	English
Article number	3
Number of pages	12
Journal	Journal of Hematology and Oncology
Volume	15
Issue number	1
Early online date	9 Jan 2022
DOIs	https://doi.org/10.1186/s13045-021-01219-7
Publication status	Published - 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).

Keywords

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
COVID
SARS-CoV-2

ASJC Scopus subject areas

Molecular Biology
Hematology
Oncology
Cancer Research

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1186/s13045-021-01219-7Licence: Creative Commons: Attribution (CC BY)

ParryH2022ImpairedFinal published version, 1.02 MBLicence: Creative Commons: Attribution (CC BY)

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Impaired Neutralisation of SARS-CoV-2 Delta Variant in Vaccinated Patients With B Cell Chronic Lymphocytic Leukaemia
Parry, H. M., Mcilroy, G., Bruton, R., Damery, S., Tyson, G., Logan, N., Davis, C., Willett, B., Zuo, J., Ali, M., Kaur, M., Stephens, C., Brant, D., Otter, A., Mcskeane, T., Rolfe, H., Faustini, S., Richter, A. G., Lee, S., Wandroo, F., & 4 othersShafeek, S., Pratt, G., Paneesha, S. & Moss, P., 12 Oct 2021, Elsevier, (SSRN Electronic Journal).
Research output: Working paper/Preprint › Preprint

Cite this

Parry, H., McIlroy, G., Moss, P., Damery, S., Tyson, G., Logan, N., Davis, C., Willett, B., Zuo, J., Ali, M., Kaur, M., Stephens, C., Brant, D., Otter, A., McSkeane, T., Rolfe, H., Faustini, S., Richter, A., Lee, S., ... Moss, P. (2022). Impaired neutralisation of SARS-CoV-2 delta variant in vaccinated patients with B cell chronic lymphocytic leukaemia. Journal of Hematology and Oncology, 15(1), Article 3. Advance online publication. https://doi.org/10.1186/s13045-021-01219-7

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

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.",

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

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: {\textcopyright} 2021, The Author(s).",

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Parry, H, McIlroy, G, Moss, P , Damery, S, Tyson, G, Logan, N, Davis, C, Willett, B, Zuo, J, Ali, M, Kaur, M, Stephens, C, Brant, D, Otter, A, McSkeane, T, Rolfe, H, Faustini, S , Richter, A, Lee, S, Wandroo, F, Shafeek, S, Pratt, G, Paneesha, S & Moss, P 2022, 'Impaired neutralisation of SARS-CoV-2 delta variant in vaccinated patients with B cell chronic lymphocytic leukaemia', Journal of Hematology and Oncology, vol. 15, no. 1, 3. https://doi.org/10.1186/s13045-021-01219-7

TY - JOUR

T1 - Impaired neutralisation of SARS-CoV-2 delta variant in vaccinated patients with B cell chronic lymphocytic leukaemia

AU - Parry, Helen

AU - McIlroy, Graham

AU - Moss, Paul

AU - Damery, Sarah

AU - Tyson, Grace

AU - Logan, Nicola

AU - Davis, Chris

AU - Willett, Brian

AU - Zuo, Jianmin

AU - Ali, Myah

AU - Kaur, Manjit

AU - Stephens, Christine

AU - Brant, Dawn

AU - Otter, Ashley

AU - McSkeane, Tina

AU - Rolfe, Hayley

AU - Faustini, Sian

AU - Richter, Alex

AU - Lee, Sophie

AU - Wandroo, Farooq

AU - Shafeek, Salim

AU - Pratt, Guy

AU - Paneesha, Shankara

AU - Moss, Paul

N1 - 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).

PY - 2022/12

Y1 - 2022/12

N2 - 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.

AB - 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.

KW - Adult

KW - Aged

KW - Aged, 80 and over

KW - Antibodies, Neutralizing/immunology

KW - Antibody Formation

KW - COVID-19 Vaccines/immunology

KW - COVID-19/complications

KW - Female

KW - HEK293 Cells

KW - Humans

KW - Leukemia, Lymphocytic, Chronic, B-Cell/complications

KW - Male

KW - Middle Aged

KW - SARS-CoV-2/immunology

KW - CLL

KW - Antibody

KW - Vaccination

KW - Leukaemia

KW - COVID

KW - SARS-CoV-2

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U2 - 10.1186/s13045-021-01219-7

DO - 10.1186/s13045-021-01219-7

M3 - Article

C2 - 35000597

SN - 1756-8722

VL - 15

JO - Journal of Hematology and Oncology

JF - Journal of Hematology and Oncology

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ER -

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

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

UN SDGs

Access to Document

Fingerprint

Research output

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

Cite this