Functionally impaired antibody response to BNT162b2 booster vaccination in CVID IgG responders.

Kai M T Sauerwein, Christoph B Geier, Roman F Stemberger, Raphael Rossmanith, Hüseyin Akyaman, Peter Illes, Michael B Fischer, Martha M Eibl, Jolan E Walter, Hermann M Wolf

Journal: The Journal of allergy and clinical immunology 2023;151(4):922-925

PMID: 36463978

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Abstract

BACKGROUND

Although previous studies described the production of IgG antibodies in a subgroup of patients with common variable immunodeficiency (CVID) following messenger RNA vaccinations with BNT162b2 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (CVID responders), the functionality of these antibodies in terms of avidity as measured by the dissociation rate constant (k) and the antibody response to booster immunization has not been studied.

OBJECTIVE

We sought to analyze in CVID responders and healthy individuals, the avidity of anti-SARS-CoV-2 serum antibodies and their neutralization capacity as measured by surrogate virus-neutralizing antibodies in addition to IgG-, IgM-, and IgA-antibody levels and the response of circulating (peripheral blood) follicular T-helper cells after a third vaccination with BNT162b2 SARS-CoV-2 messenger RNA vaccine.

METHODS

Binding IgG, IgA, and IgM serum levels were analyzed by ELISA in patients with CVID responding to the primary vaccination (CVID responders, n = 10) and healthy controls (n = 41). The binding avidity of anti-spike antibodies was investigated using biolayer interferometry in combination with biotin-labeled receptor-binding-domain of SARS-CoV-2 spike protein and streptavidin-labeled sensors. Antigen-specific recall T-cell responses were assessed by measuring activation-induced markers by flow cytometry.

RESULTS

After the third vaccination with BNT162b2, IgG-, IgM-, and IgA-antibody levels, surrogate virus-neutralizing antibody levels, and antibody avidity were lower in CVID responders than in healthy controls. In contrast, anti-SARS-CoV-2 spike protein avidity was comparable in CVID responders and healthy individuals following primary vaccination. Follicular T-helper cell response to booster vaccination in CVID responders was significantly reduced when compared with that in healthy individuals.

CONCLUSIONS

Impaired affinity maturation during booster response provides new insight into CVID pathophysiology.

Address: Immunology Outpatient Clinic, Vienna, Austria; Biomedizinische Forschung & Bio-Produkte AG, Vienna, Austria; Department for Biomedical Research, Center of Experimental Medicine, Danube University Krems, Krems an der Donau, Austria.; Immunology Outpatient Clinic, Vienna, Austria.; USF Health Department of Pediatrics, Division of Allergy/Immunology, Children's Research Institute, St Petersburg, Fla.; Department for Biomedical Research, Center of Experimental Medicine, Danube University Krems, Krems an der Donau, Austria; Clinic for Blood Group Serology and Transfusion Medicine, Medical University of Vienna, Vienna, Austria.; Immunology Outpatient Clinic, Vienna, Austria; Biomedizinische Forschung & Bio-Produkte AG, Vienna, Austria.; Division of Allergy and Immunology, Department of Pediatrics, Morsani College of Medicine, University of South Florida, Tampa, Fla; Division of Allergy/Immunology, Department of Pediatrics, Johns Hopkins All Children's Hospital, St Petersburg, Fla.; Immunology Outpatient Clinic, Vienna, Austria; Sigmund Freud Private University, Medical School, Vienna, Austria. Electronic address: [email protected].

DOI: 10.1016/j.jaci.2022.11.013

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MeSH Terms: Humans, BNT162 Vaccine, Common Variable Immunodeficiency, Antibody Formation, COVID-19, SARS-CoV-2, Spike Glycoprotein, Coronavirus, COVID-19 Vaccines, Antibodies, Blocking, Antibodies, Viral, Immunoglobulin A, Immunoglobulin M