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
N1 - Publisher Copyright:
© 2022, The Author(s).
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 - http://www.scopus.com/inward/record.url?scp=85128253099&partnerID=8YFLogxK
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 -
