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


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-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.


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.


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.


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

Author list



  1. Clinical Immunology Service, Institute for Immunology and Immunotherapy, University of Birmingham, UK
  2. University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
  3. Department of Immunology and Allergy, University Hospital Plymouth NHS Trust, Plymouth, UK
  4. Department of Clinical Immunology, Oxford University Hospitals NHS Foundation Trust, Oxford, UK
  5. Department of Immunology, Salford Royal NHS Foundation Trust, Salford, UK
  6. Department of Immunology, North Bristol NHS Trust, Bristol, UK 
  7. Saving Lives Charity, MIDRU Building, Heartlands Hospital,Birmingham, UK
  8. Institute of Translational Medicine, University of Birmingham, Birmingham, UK
  9. Department of Immunology, University Hospital North Midlands, Stoke, UK
  10. Newcastle Upon Tyne Hospitals NHS Foundation Trust, New- castle, UK
  11. Department of Allergy and Clinical Immunology, Leeds Teaching Hospitals NHS Trust, Leeds, UK
  12. Research and Development Department, University Hospital Plymouth NHS Trust, Plymouth, UK


Adrian M. Shields1,2  Sian E. Faustini1  Harriet J. Hill3  Saly Al‐Taei1  Chloe Tanner1  Fiona Ashford1  Sarita Workman4  Fernando Moreira4  Nisha Verma4  Hollie Wagg5  Gail Heritage5  Naomi Campton5  Zania Stamataki3  Paul Klenerman6  James E. D. Thaventhiran7  Sarah Goddard8  Sarah Johnston9  Aarnoud Huissoon2  Claire Bethune10  Suzanne Elcombe11  David M. Lowe4,12  Smita Y. Patel6,13  Sinisa Savic14  Siobhan O. Burns4,12  Alex G. Richter1,2  on behalf of the COV‐AD consortium

Novel Coronavirus SARS-CoV-2


Journal of Clinical Immunology