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SARS-CoV-2 Vaccine Responses in Individuals with Antibody Deficiency: Findings from the COV-AD Study |
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| Authors: | Shields Adrian M Faustini Sian E Hill Harriet J Al-Taei Saly Tanner Chloe Ashford Fiona Workman Sarita Moreira Fernando Verma Nisha Wagg Hollie Heritage Gail Campton Naomi Stamataki Zania Klenerman Paul Thaventhiran James E D Goddard Sarah Johnston Sarah Huissoon Aarnoud Bethune Claire Elcombe Suzanne Lowe David M Patel Smita Y Savic Sinisa Burns Siobhan O Richter Alex G |
| Institution: | 1.Clinical Immunology Service, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK ;2.University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK ;3.Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK ;4.Department of Immunology, Royal Free London NHS Foundation Trust, London, UK ;5.Institute of Translational Medicine, University of Birmingham, Birmingham, UK ;6.Nuffield Department of Medicine, University of Oxford, Oxford, UK ;7.Medical Research Council Toxicology Unit, University of Cambridge, Gleeson Building, Tennis Court Road, Cambridge, CB2 1QW, UK ;8.Department of Clinical Immunology, University Hospitals North Midlands, Stoke-on-Trent, UK ;9.Department of Clinical Immunology, North Bristol NHS Trust, Bristol, UK ;10.Department of Allergy and Clinical Immunology, University Hospitals Plymouth NHS Trust, Plymouth, UK ;11.Department of Allergy and Clinical Immunology, Newcastle Upon Tyne Hospitals NHS Foundation Trust, Newcastle, UK ;12.Institute of Immunity and Transplantation, University College London, London, UK ;13.NIHR BRC Oxford Biomedical Centre, University of Oxford, Oxford, UK ;14.Department of Allergy and Clinical Immunology, Leeds Teaching Hospitals NHS Trust, Leeds, 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. ObjectivesCOVID-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. MethodsIndividuals 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. ResultsA 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. ConclusionSARS-CoV-2 vaccines demonstrate reduced immunogenicity in patients with antibody deficiency with evidence of vaccine breakthrough infection. |
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