Author:
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.,Ahmed Zahra,Bancroft Hollie,Bates Michelle,Clifford Hayley,Davis Georgina,Dasgin Joanne,Dinally Mohammad,Dhalla Fatima,Efstathiou Elena,Elkhalifa Shuayb,Gompels Mark,Hartland Dan,Hoque Madeeha,Heritage Emily,Hughes Deborah,Ivory Ann,Jain Rashmi,Kelly Sinead,McCarthy Theresa,McGee Christopher,Mullan Daniel,Morsi Hadeil,O’Grady Eileen,Page Shannon,Peters Nicholas,Plant Timothy,Shajidevadas Archana,Slowinsksa Malgorzata,Suleiman Zehra,Townsend Neil,Trinham Charlotte,Wareham Stuart,Walder Sinead,
Abstract
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.
Funder
UK Research and Innovation
Publisher
Springer Science and Business Media LLC
Subject
Immunology,Immunology and Allergy