SARS-CoV-2 vaccine responses in individuals with antibody deficiency: findings from the COV-AD study.
Shields, Adrian M Faustini, Sian E Hill, Harriet J Al-Taei, Saly Tanner, Chloe Ashford, Fiona Workman, Sarita Moreira, Fernando Verma, Nisha Wagg, Hollie
Shields, Adrian M
Faustini, Sian E
Hill, Harriet J
Al-Taei, Saly
Tanner, Chloe
Ashford, Fiona
Workman, Sarita
Moreira, Fernando
Verma, Nisha
Wagg, Hollie
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2022-04-14
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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.
Citation
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; COV-AD consortium. 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
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