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

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

JOURNAL=Frontiers in Immunology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.934476

DOI=10.3389/fimmu.2022.934476

ISSN=1664-3224

ABSTRACT=<sec><title>Background</title><p>The antibody response after vaccination is impaired in common variable immunodeficiency (CVID).</p></sec><sec><title>Objective</title><p>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.</p></sec><sec><title>Methods</title><p>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 &lt; 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.</p></sec><sec><title>Results</title><p>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], <italic>p</italic> = 0.006) and tended to increase after the fourth dose (193 BAU/ml, [−22; 569 BAU/ml], <italic>p</italic> = 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 (<italic>p</italic> = 0.009). IgRT products had varying concentrations of anti-S-RBD (<italic>p</italic> &lt; 0.001), but none of the products seemed to affect the overall antibody levels (<italic>p</italic> = 0.460).</p></sec><sec><title>Conclusion</title><p>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.</p></sec><sec><title>Clinical Implications</title><p>Boosting with SARS-CoV-2 vaccines seems to improve the antibody response in CVID patients.</p></sec><sec><title>Capsule summary</title><p>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.</p></sec>