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Antibody response following the third and fourth SARS-CoV-2 vaccine dose in individuals with common variable immunodeficiency

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Background: The antibody response after vaccination is impaired in common variable immunodeficiency (CVID).

Objective: We aimed to study the spike receptor-binding domain IgG antibody (anti-S-RBD) levels during a four-dose SARS-CoV-2 vaccination strategy and after monoclonal antibody (mAB) treatment in CVID. Moreover, we assessed the anti-S-RBD levels in immunoglobulin replacement therapy (IgRT) products.

Methods: In an observational study, we examined anti-S-RBD levels after the second, third, and fourth dose of mRNA SARS-CoV-2 vaccines. Moreover, we measured anti-S-RBD after treatment with mAB. Finally, anti-S-RBD was assessed in common IgRT products. Antibody non-responders (anti-S-RBD < 7.1) were compared by McNemar's test and anti-S-RBD levels were compared with paired and non-paired Wilcoxon signed rank tests as well as Kruskal-Wallis tests.

Results: Among 33 individuals with CVID, anti-S-RBD levels increased after the third vaccine dose (165 BAU/ml [95% confidence interval: 85; 2280 BAU/ml], p = 0.006) and tended to increase after the fourth dose (193 BAU/ml, [-22; 569 BAU/ml], p = 0.080) compared to the previous dose. With increasing number of vaccinations, the proportion of patients who seroconverted (anti-S-RBD ≥ 7.1) increased non-significantly. mAB treatment resulted in a large increase in anti-S-RBD and a higher median level than gained after the fourth dose of vaccine (p = 0.009). IgRT products had varying concentrations of anti-S-RBD (p < 0.001), but none of the products seemed to affect the overall antibody levels (p = 0.460).

Conclusion: Multiple SARS-CoV-2 vaccine doses in CVID seem to provide additional protection, as antibody levels increased after the third and fourth vaccine dose. However, anti-S-RBD levels from mAB outperform the levels mounted after vaccination.

Clinical Implications: Boosting with SARS-CoV-2 vaccines seems to improve the antibody response in CVID patients.

Capsule summary: The third and possibly also the fourth dose of mRNA SARS-CoV-2 vaccine in CVID improve the antibody response as well as stimulate seroconversion in most non-responders.

Original languageEnglish
Article number934476
JournalFrontiers in Immunology
Volume13
Pages (from-to)934476
ISSN1664-3224
DOIs
Publication statusPublished - 2022

Bibliographical note

Copyright © 2022 Nielsen, Drabe, Barnkob, Johansen, Hansen, Nilsson and Rasmussen.

    Research areas

  • Antibody Formation, COVID-19/prevention & control, COVID-19 Vaccines, Common Variable Immunodeficiency/therapy, Humans, RNA, Messenger, SARS-CoV-2, Viral Vaccines

ID: 80511714