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

Bibi Uhre Nielsen, Camilla Heldbjerg Drabe, Mike Bogetofte Barnkob, Isik Somuncu Johansen, Anne Kirstine Kronborg Hansen, Anna Christine Nilsson, Line Dahlerup Rasmussen*

*Corresponding author for this work

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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
Number of pages9
Publication statusPublished - 28. Jul 2022

Bibliographical note

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


  • booster doses
  • corona vaccination
  • covid-19
  • cvid
  • sars-cov2
  • Common Variable Immunodeficiency/therapy
  • Humans
  • SARS-CoV-2
  • COVID-19 Vaccines
  • Viral Vaccines
  • Antibody Formation
  • COVID-19/prevention & control
  • RNA, Messenger


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