Functionally impaired antibody response to BNT162b2 booster vaccination in CVID IgG responders - 05/04/23
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 (kdis) 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.
Il testo completo di questo articolo è disponibile in PDF.Key words : BNT162b2 booster vaccination, CVID, antibody avidity, cTfh, biolayer interferometry
Abbreviations used : αSpike, cTfh, CVID, CVID R, HC, IQR, IVIG, kdis, SARS-CoV-2, sVNT
Mappa
| This study was supported by the Österreichische Forschungsförderungsgesellschaft mbH (grant no. 881639), and by the Jeffrey Modell Foundation, the Johns Hopkins Research Foundation, and the Robert A. Good Endowment. |
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| Ethics statement: The study was conducted in accordance with the Declaration of Helsinki and fulfils the guidelines of the Austrian Agency of Research Integrity (OeAWI). With respect to the patient analyses, this study was approved by the Ethics Committee of the Immunology Outpatient Clinic as a study using the biobank of residual specimen of the Immunology Outpatient Clinic. According to the Ethics Committee of the City of Vienna and the legal regulations to be applied (§15a Abs. 3a Wiener Krankenanstaltengesetz), no additional ethics committee evaluation is required for a noninterventional study using data and material collected as part of the routine medical care the patients received. The patients gave their informed consent that anonymized data collected as part of the routine medical attendance (serum antibody measurements and T-cell activation assays) could be included in a scientific publication. All patient information in this study is anonymized and deidentified. No extra intervention was carried out. |
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| Disclosure of potential conflict of interest: K. M. T. Sauerwein and M. M. Eibl were employed by the company Biomedizinische Forschung & Bio-Produkte AG, which had no role in the design of this study or during its execution, and was not involved in the analyses, interpretation of the data, and the decision to submit the present manuscript for publication. The rest of the authors declare that they have no relevant conflicts of interest. |
Vol 151 - N° 4
P. 922-925 - Aprile 2023 Ritorno al numero
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