Related Experiment Video
Updated: Sep 27, 2025
Detection of SARS-CoV-2 Neutralizing Antibodies using High-Throughput Fluorescent Imaging of Pseudovirus Infection
Published on: June 5, 2021
SARS-CoV-2 Vaccine Responses in Individuals with Antibody Deficiency: Findings from the COV-AD Study
Adrian M Shields1,2, Sian E Faustini3, Harriet J Hill4
1Clinical Immunology Service, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK. a.m.shields@bham.ac.uk.
Insights
COVID-19 vaccines show reduced effectiveness in patients with antibody deficiency. These individuals had lower seropositivity and neutralizing antibody levels after vaccination, with some experiencing breakthrough infections.
Area of Science:
- Immunology
- Vaccinology
- Infectious Diseases
Background:
- Antibody deficiency compromises immune response to infections and vaccinations.
- The immunogenicity and efficacy of SARS-CoV-2 vaccines in this population are not well understood.
Purpose of the Study:
- To assess the immune response to SARS-CoV-2 infection and vaccination in patients with primary or secondary antibody deficiency.
- To evaluate vaccine efficacy and identify factors influencing response in this vulnerable group.
Main Methods:
- Recruited patients on immunoglobulin therapy or with low IgG levels.
- Measured serological (ELISA, neutralization) and cellular (interferon gamma release) responses.
- Monitored SARS-CoV-2 infection and clearance via PCR.
Main Results:
- Only 54.8% seropositivity post-vaccination in antibody deficient patients versus 100% in controls.
- Reduced antibody magnitude and neutralizing capacity observed.
- Pfizer/BioNTech showed higher seropositivity and antibody levels than AstraZeneca.
- T cell responses were present in 46.2% and associated with better antibody response.
- Eleven vaccine breakthrough infections occurred, mostly with AstraZeneca.
Conclusions:
- SARS-CoV-2 vaccines are less immunogenic in patients with antibody deficiency.
- Evidence of vaccine breakthrough infections highlights the need for further strategies in this population.
- Vaccine choice may influence serological response, with Pfizer/BioNTech appearing more effective.
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.
More Related Videos
Related Concept Videos
01:36Humoral Immune Responses
01:25Immunodeficiency Diseases
There are three main causes of immunodeficiency...
01:26Antigens Involved in Adaptive Immunity
Complete Antigens
Complete antigens possess both immunogenicity and...
01:29Immune Response Against Viral Pathogens
NK Cells
NK cells are a crucial part of our innate immune system, acting as the first line of defense against viral infections. These cells can recognize and kill infected cells without prior exposure to the virus, effectively slowing down the spread of infection. Additionally, NK cells produce proinflammatory...
01:22Development of Immunocompetence
The initial cells that migrate from the fetal thymus settle within the skin and epithelial tissues lining the mouth, digestive tract, and in females, the uterus and vagina. These cells, including skin-based dendritic cells, serve as antigen-presenting cells, playing a key role in T cell activation.
Subsequent T...
00:42Cross-reactivity