SARS-CoV-2 Vaccine Responses in Individuals with Antibody Deficiency: Findings from the COV-AD Study

COV-AD consortium; Adrian M. Shields; Sian E. Faustini; Harriet J. Hill; Saly Al-taei; Chloe Tanner; Fiona Ashford; Sarita Workman; Fernando Moreira; Nisha Verma; Hollie Wagg; Gail Heritage; Naomi Campton; Zania Stamataki; Paul Klenerman; James E. D. Thaventhiran; Sarah Goddard; Sarah Johnston; Aarnoud Huissoon; Claire Bethune; Suzanne Elcombe; David M. Lowe; Smita Y. Patel; Sinisa Savic; Siobhan O. Burns; Alex G. Richter

doi:10.1007/s10875-022-01231-7

SARS-CoV-2 Vaccine Responses in Individuals with Antibody Deficiency: Findings from the COV-AD Study

COV-AD consortium
, Adrian M. Shields^*
, Sian E. Faustini
, Harriet J. Hill
, Saly Al-taei
, Chloe Tanner
, Fiona Ashford
, Sarita Workman
, Fernando Moreira
, Nisha Verma
, Hollie Wagg
, Gail Heritage
, Naomi Campton
, Zania Stamataki
, Paul Klenerman
, James E. D. Thaventhiran
, Sarah Goddard
, Sarah Johnston
, Aarnoud Huissoon
, Claire Bethune

Suzanne Elcombe, David M. Lowe, Smita Y. Patel, Sinisa Savic, Siobhan O. Burns, Alex G. Richter

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

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Abstract

Background: Vaccination prevents severe morbidity and mortality from COVID-19 in the general population. The immunogenicity and efficacy of SARS-CoV-2 vaccines in patients with antibody deficiency is poorly understood. Objectives: COVID-19 in patients with antibody deficiency (COV-AD) is a multi-site UK study that aims to determine the immune response to SARS-CoV-2 infection and vaccination in patients with primary or secondary antibody deficiency, a population that suffers from severe and recurrent infection and does not respond well to vaccination. Methods: Individuals on immunoglobulin replacement therapy or with an IgG less than 4 g/L receiving antibiotic prophylaxis were recruited from April 2021. Serological and cellular responses were determined using ELISA, live-virus neutralisation and interferon gamma release assays. SARS-CoV-2 infection and clearance were determined by PCR from serial nasopharyngeal swabs. Results: A total of 5.6% (n = 320) of the cohort reported prior SARS-CoV-2 infection, but only 0.3% remained PCR positive on study entry. Seropositivity, following two doses of SARS-CoV-2 vaccination, was 54.8% (n = 168) compared with 100% of healthy controls (n = 205). The magnitude of the antibody response and its neutralising capacity were both significantly reduced compared to controls. Participants vaccinated with the Pfizer/BioNTech vaccine were more likely to be seropositive (65.7% vs. 48.0%, p = 0.03) and have higher antibody levels compared with the AstraZeneca vaccine (IgGAM ratio 3.73 vs. 2.39, p = 0.0003). T cell responses post vaccination was demonstrable in 46.2% of participants and were associated with better antibody responses but there was no difference between the two vaccines. Eleven vaccine-breakthrough infections have occurred to date, 10 of them in recipients of the AstraZeneca vaccine. Conclusion: SARS-CoV-2 vaccines demonstrate reduced immunogenicity in patients with antibody deficiency with evidence of vaccine breakthrough infection.

Original language	English
Pages (from-to)	923-934
Number of pages	12
Journal	Journal of Clinical Immunology
Volume	42
Issue number	5
Early online date	14 Apr 2022
DOIs	https://doi.org/10.1007/s10875-022-01231-7
Publication status	Published - Jul 2022

Bibliographical note

Publisher Copyright:
© 2022, The Author(s).

UN SDGs

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

SDG 3 Good Health and Well-being

Keywords

COVID-19
CVID
Inborn errors of immunity
Primary immunodeficiency
SARS-CoV-2
Secondary immunodeficienc
Vaccination
Secondary immunodeficiency

ASJC Scopus subject areas

Immunology and Allergy
Immunology

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ShieldsA2022SARSFinal published version, 834 KBLicence: Creative Commons: Attribution (CC BY)

Cite this

COV-AD consortium, Shields, A. M., Faustini, S. E., Hill, H. J., Al-taei, S., Tanner, C., Ashford, F., Workman, S., Moreira, F., Verma, N., Wagg, H., Heritage, G., Campton, N., Stamataki, Z., Klenerman, P., Thaventhiran, J. E. D., Goddard, S., Johnston, S., Huissoon, A., ... Richter, A. G. (2022). SARS-CoV-2 Vaccine Responses in Individuals with Antibody Deficiency: Findings from the COV-AD Study. Journal of Clinical Immunology, 42(5), 923-934. https://doi.org/10.1007/s10875-022-01231-7

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title = "SARS-CoV-2 Vaccine Responses in Individuals with Antibody Deficiency: Findings from the COV-AD Study",

abstract = "Background: Vaccination prevents severe morbidity and mortality from COVID-19 in the general population. The immunogenicity and efficacy of SARS-CoV-2 vaccines in patients with antibody deficiency is poorly understood. Objectives: COVID-19 in patients with antibody deficiency (COV-AD) is a multi-site UK study that aims to determine the immune response to SARS-CoV-2 infection and vaccination in patients with primary or secondary antibody deficiency, a population that suffers from severe and recurrent infection and does not respond well to vaccination. Methods: Individuals on immunoglobulin replacement therapy or with an IgG less than 4 g/L receiving antibiotic prophylaxis were recruited from April 2021. Serological and cellular responses were determined using ELISA, live-virus neutralisation and interferon gamma release assays. SARS-CoV-2 infection and clearance were determined by PCR from serial nasopharyngeal swabs. Results: A total of 5.6\% (n = 320) of the cohort reported prior SARS-CoV-2 infection, but only 0.3\% remained PCR positive on study entry. Seropositivity, following two doses of SARS-CoV-2 vaccination, was 54.8\% (n = 168) compared with 100\% of healthy controls (n = 205). The magnitude of the antibody response and its neutralising capacity were both significantly reduced compared to controls. Participants vaccinated with the Pfizer/BioNTech vaccine were more likely to be seropositive (65.7\% vs. 48.0\%, p = 0.03) and have higher antibody levels compared with the AstraZeneca vaccine (IgGAM ratio 3.73 vs. 2.39, p = 0.0003). T cell responses post vaccination was demonstrable in 46.2\% of participants and were associated with better antibody responses but there was no difference between the two vaccines. Eleven vaccine-breakthrough infections have occurred to date, 10 of them in recipients of the AstraZeneca vaccine. Conclusion: SARS-CoV-2 vaccines demonstrate reduced immunogenicity in patients with antibody deficiency with evidence of vaccine breakthrough infection.",

keywords = "COVID-19, CVID, Inborn errors of immunity, Primary immunodeficiency, SARS-CoV-2, Secondary immunodeficienc, Vaccination, Secondary immunodeficiency",

author = "\{COV-AD consortium\} and Shields, \{Adrian M.\} and Faustini, \{Sian E.\} and Hill, \{Harriet J.\} and Saly Al-taei and Chloe Tanner and Fiona Ashford and Sarita Workman and Fernando Moreira and Nisha Verma and Hollie Wagg and Gail Heritage and Naomi Campton and Zania Stamataki and Paul Klenerman and Thaventhiran, \{James E. D.\} and Sarah Goddard and Sarah Johnston and Aarnoud Huissoon and Claire Bethune and Suzanne Elcombe and Lowe, \{David M.\} and Patel, \{Smita Y.\} and Sinisa Savic and Burns, \{Siobhan O.\} and Richter, \{Alex G.\} and Zahra Ahmed and Hollie Bancroft and Michelle Bates and Hayley Clifford and Georgina Davis and Joanne Dasgin and Mohammad Dinally and Fatima Dhalla and Elena Efstathiou and Shuayb Elkhalifa and Mark Gompels and Dan Hartland and Madeeha Hoque and Emily Heritage and Deborah Hughes and Ann Ivory and Rashmi Jain and Sinead Kelly and Theresa Mccarthy and Christopher Mcgee and Daniel Mullan and Hadeil Morsi and Eileen O{\textquoteright}grady and Shannon Page and Timothy Plant and Archana Shajidevadas and Malgorzata Slowinsksa and Zehra Suleiman and Neil Townsend and Charlotte Trinham and Stuart Wareham and Sinead Walder",

note = "Publisher Copyright: {\textcopyright} 2022, The Author(s).",

year = "2022",

month = jul,

doi = "10.1007/s10875-022-01231-7",

language = "English",

volume = "42",

pages = "923--934",

journal = "Journal of Clinical Immunology",

issn = "0271-9142",

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COV-AD consortium, Shields, AM , Faustini, SE, Hill, HJ, Al-taei, S, Tanner, C, Ashford, F, Workman, S, Moreira, F, Verma, N, Wagg, H, Heritage, G, Campton, N, Stamataki, Z, Klenerman, P, Thaventhiran, JED, Goddard, S, Johnston, S, Huissoon, A, Bethune, C, Elcombe, S, Lowe, DM, Patel, SY, Savic, S, Burns, SO & Richter, AG 2022, 'SARS-CoV-2 Vaccine Responses in Individuals with Antibody Deficiency: Findings from the COV-AD Study', Journal of Clinical Immunology, vol. 42, no. 5, pp. 923-934. https://doi.org/10.1007/s10875-022-01231-7

TY - JOUR

T1 - SARS-CoV-2 Vaccine Responses in Individuals with Antibody Deficiency

T2 - Findings from the COV-AD Study

AU - COV-AD consortium

AU - Shields, Adrian M.

AU - Faustini, Sian E.

AU - Hill, Harriet J.

AU - Al-taei, Saly

AU - Tanner, Chloe

AU - Ashford, Fiona

AU - Workman, Sarita

AU - Moreira, Fernando

AU - Verma, Nisha

AU - Wagg, Hollie

AU - Heritage, Gail

AU - Campton, Naomi

AU - Stamataki, Zania

AU - Klenerman, Paul

AU - Thaventhiran, James E. D.

AU - Goddard, Sarah

AU - Johnston, Sarah

AU - Huissoon, Aarnoud

AU - Bethune, Claire

AU - Elcombe, Suzanne

AU - Lowe, David M.

AU - Patel, Smita Y.

AU - Savic, Sinisa

AU - Burns, Siobhan O.

AU - Richter, Alex G.

AU - Ahmed, Zahra

AU - Bancroft, Hollie

AU - Bates, Michelle

AU - Clifford, Hayley

AU - Davis, Georgina

AU - Dasgin, Joanne

AU - Dinally, Mohammad

AU - Dhalla, Fatima

AU - Efstathiou, Elena

AU - Elkhalifa, Shuayb

AU - Gompels, Mark

AU - Hartland, Dan

AU - Hoque, Madeeha

AU - Heritage, Emily

AU - Hughes, Deborah

AU - Ivory, Ann

AU - Jain, Rashmi

AU - Kelly, Sinead

AU - Mccarthy, Theresa

AU - Mcgee, Christopher

AU - Mullan, Daniel

AU - Morsi, Hadeil

AU - O’grady, Eileen

AU - Page, Shannon

AU - Plant, Timothy

AU - Shajidevadas, Archana

AU - Slowinsksa, Malgorzata

AU - Suleiman, Zehra

AU - Townsend, Neil

AU - Trinham, Charlotte

AU - Wareham, Stuart

AU - Walder, Sinead

PY - 2022/7

Y1 - 2022/7

N2 - Background: Vaccination prevents severe morbidity and mortality from COVID-19 in the general population. The immunogenicity and efficacy of SARS-CoV-2 vaccines in patients with antibody deficiency is poorly understood. Objectives: COVID-19 in patients with antibody deficiency (COV-AD) is a multi-site UK study that aims to determine the immune response to SARS-CoV-2 infection and vaccination in patients with primary or secondary antibody deficiency, a population that suffers from severe and recurrent infection and does not respond well to vaccination. Methods: Individuals on immunoglobulin replacement therapy or with an IgG less than 4 g/L receiving antibiotic prophylaxis were recruited from April 2021. Serological and cellular responses were determined using ELISA, live-virus neutralisation and interferon gamma release assays. SARS-CoV-2 infection and clearance were determined by PCR from serial nasopharyngeal swabs. Results: A total of 5.6% (n = 320) of the cohort reported prior SARS-CoV-2 infection, but only 0.3% remained PCR positive on study entry. Seropositivity, following two doses of SARS-CoV-2 vaccination, was 54.8% (n = 168) compared with 100% of healthy controls (n = 205). The magnitude of the antibody response and its neutralising capacity were both significantly reduced compared to controls. Participants vaccinated with the Pfizer/BioNTech vaccine were more likely to be seropositive (65.7% vs. 48.0%, p = 0.03) and have higher antibody levels compared with the AstraZeneca vaccine (IgGAM ratio 3.73 vs. 2.39, p = 0.0003). T cell responses post vaccination was demonstrable in 46.2% of participants and were associated with better antibody responses but there was no difference between the two vaccines. Eleven vaccine-breakthrough infections have occurred to date, 10 of them in recipients of the AstraZeneca vaccine. Conclusion: SARS-CoV-2 vaccines demonstrate reduced immunogenicity in patients with antibody deficiency with evidence of vaccine breakthrough infection.

AB - Background: Vaccination prevents severe morbidity and mortality from COVID-19 in the general population. The immunogenicity and efficacy of SARS-CoV-2 vaccines in patients with antibody deficiency is poorly understood. Objectives: COVID-19 in patients with antibody deficiency (COV-AD) is a multi-site UK study that aims to determine the immune response to SARS-CoV-2 infection and vaccination in patients with primary or secondary antibody deficiency, a population that suffers from severe and recurrent infection and does not respond well to vaccination. Methods: Individuals on immunoglobulin replacement therapy or with an IgG less than 4 g/L receiving antibiotic prophylaxis were recruited from April 2021. Serological and cellular responses were determined using ELISA, live-virus neutralisation and interferon gamma release assays. SARS-CoV-2 infection and clearance were determined by PCR from serial nasopharyngeal swabs. Results: A total of 5.6% (n = 320) of the cohort reported prior SARS-CoV-2 infection, but only 0.3% remained PCR positive on study entry. Seropositivity, following two doses of SARS-CoV-2 vaccination, was 54.8% (n = 168) compared with 100% of healthy controls (n = 205). The magnitude of the antibody response and its neutralising capacity were both significantly reduced compared to controls. Participants vaccinated with the Pfizer/BioNTech vaccine were more likely to be seropositive (65.7% vs. 48.0%, p = 0.03) and have higher antibody levels compared with the AstraZeneca vaccine (IgGAM ratio 3.73 vs. 2.39, p = 0.0003). T cell responses post vaccination was demonstrable in 46.2% of participants and were associated with better antibody responses but there was no difference between the two vaccines. Eleven vaccine-breakthrough infections have occurred to date, 10 of them in recipients of the AstraZeneca vaccine. Conclusion: SARS-CoV-2 vaccines demonstrate reduced immunogenicity in patients with antibody deficiency with evidence of vaccine breakthrough infection.

KW - COVID-19

KW - CVID

KW - Inborn errors of immunity

KW - Primary immunodeficiency

KW - SARS-CoV-2

KW - Secondary immunodeficienc

KW - Vaccination

KW - Secondary immunodeficiency

UR - https://www.scopus.com/pages/publications/85128253099

U2 - 10.1007/s10875-022-01231-7

DO - 10.1007/s10875-022-01231-7

M3 - Article

C2 - 35420363

SN - 0271-9142

VL - 42

SP - 923

EP - 934

JO - Journal of Clinical Immunology

JF - Journal of Clinical Immunology

IS - 5

ER -

SARS-CoV-2 Vaccine Responses in Individuals with Antibody Deficiency: Findings from the COV-AD Study

Abstract

Bibliographical note

UN SDGs

Keywords

ASJC Scopus subject areas

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