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

This research has not been peer-reviewed. It is a preliminary report that should not be regarded as conclusive, guide clinical practice or health-related behaviour, or be reported in news media as established information.


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.


COVID in patients with antibody deficiency (COV-AD) is a multi-site United Kingdom 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.


Individuals on immunoglobulin replacement therapy or with an IgG less than 4g/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.


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 were demonstrable in 46.2% of participants, 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.


SARS-CoV-2 vaccines demonstrate reduced immunogenicity in patients with antibody deficiency with evidence of vaccine breakthrough infection.

Author list

Adrian M Shields, University of Birmingham

Sian E. Faustini, University of Birmingham, 

Harriet J. Hill, University of Birmingham, 

Saly Al-Taei, University of Birmingham, 

Chloe Tanner, University of Birmingham

Fiona Ashford, University of Birmingham

Sarita Workman, Department of Immunology, Royal Free London NHS Foundation Trust

Fernando Moreira, Department of Immunology, Royal Free London NHS Foundation Trust

Nisha Verma, Department of Immunology, Royal Free London NHS Foundation Trust

Hollie Wagg, University of Birmingham

Gail Heritage, University of Birmingham

Naomi Campton, University of Birmingham

Zania Stamataki, University of Birmingham

Paul Klenerman, University of Oxford

Sarah Goddard, University Hospitals North Midlands

Sarah Johnston, Department of Clinical Immunology, North Bristol NHS Trust

Aarnoud Huissoon, University Hospitals Birmingham NHS Foundation Trust

Claire Bethune,, University Hospitals Plymouth NHS Trust

Suzanne Elcombe, Department of Allergy and Clinical Immunology, Newcastle upon Tyne Hospitals NHS Foundation Trust

David M. Lowe, Department of Immunology, Royal Free London NHS Foundation Trust

Smita Y. Patel, University of Oxford

Sinisa Savic, Department of Allergy and Clinical Immunology, Leeds Teaching Hospitals NHS Trust

Siobhan O. Burns, Department of Immunology, Royal Free London NHS Foundation Trust

Alex G. Richter, University of Birmingham

COV-AD Consortium


Novel Coronavirus SARS-CoV-2


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