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

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; COV-AD consortium

doi:10.1007/s10875-022-01231-7

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

J Clin Immunol. 2022 Jul;42(5):923-934. doi: 10.1007/s10875-022-01231-7. Epub 2022 Apr 14.

Authors

Adrian M Shields^{1

2}, Sian E Faustini³, Harriet J Hill⁴, Saly Al-Taei³, Chloe Tanner³, Fiona Ashford³, Sarita Workman⁵, Fernando Moreira⁵, Nisha Verma⁵, Hollie Wagg⁶, Gail Heritage⁶, Naomi Campton⁶, Zania Stamataki⁴, Paul Klenerman⁷, James E D Thaventhiran⁸, Sarah Goddard⁹, Sarah Johnston¹⁰, Aarnoud Huissoon¹¹, Claire Bethune¹², Suzanne Elcombe¹³, David M Lowe^{5

14}, Smita Y Patel^{7

15}, Sinisa Savic¹⁶, Siobhan O Burns^{17

18}, Alex G Richter^{19

20}; COV-AD consortium

Affiliations

¹ Clinical Immunology Service, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK. a.m.shields@bham.ac.uk.
² University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK. a.m.shields@bham.ac.uk.
³ Clinical Immunology Service, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK.
⁴ Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK.
⁵ Department of Immunology, Royal Free London NHS Foundation Trust, London, UK.
⁶ Institute of Translational Medicine, University of Birmingham, Birmingham, UK.
⁷ Nuffield Department of Medicine, University of Oxford, Oxford, UK.
⁸ Medical Research Council Toxicology Unit, University of Cambridge, Gleeson Building, Tennis Court Road, Cambridge, CB2 1QW, UK.
⁹ Department of Clinical Immunology, University Hospitals North Midlands, Stoke-on-Trent, UK.
¹⁰ Department of Clinical Immunology, North Bristol NHS Trust, Bristol, UK.
¹¹ University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK.
¹² Department of Allergy and Clinical Immunology, University Hospitals Plymouth NHS Trust, Plymouth, UK.
¹³ Department of Allergy and Clinical Immunology, Newcastle Upon Tyne Hospitals NHS Foundation Trust, Newcastle, UK.
¹⁴ Institute of Immunity and Transplantation, University College London, London, UK.
¹⁵ NIHR BRC Oxford Biomedical Centre, University of Oxford, Oxford, UK.
¹⁶ Department of Allergy and Clinical Immunology, Leeds Teaching Hospitals NHS Trust, Leeds, UK.
¹⁷ Department of Immunology, Royal Free London NHS Foundation Trust, London, UK. siobhan.burns@ucl.ac.uk.
¹⁸ Institute of Immunity and Transplantation, University College London, London, UK. siobhan.burns@ucl.ac.uk.
¹⁹ Clinical Immunology Service, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK. a.g.richter@bham.ac.uk.
²⁰ University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK. a.g.richter@bham.ac.uk.

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 immunodeficiency; Vaccination.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antibodies, Viral
COVID-19 Vaccines
COVID-19*
Humans
Primary Immunodeficiency Diseases*
SARS-CoV-2
Viral Vaccines*

Substances

Antibodies, Viral
COVID-19 Vaccines
Viral Vaccines

Grants and funding

MRF_MRF-169-0001-F-STAM-C0826/MRF/MRF/United Kingdom