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

Abstract

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.

Keywords: booster doses; corona vaccination; covid-19; cvid; sars-cov2.

Figure 1

Proportion of individuals with common variable immunodeficiency within each category of anti-spike protein receptor-binding domain IgG antibody response after different doses of SARS-CoV-2 vaccination. Samples were collected from 27 individuals with common variable immunodeficiency. Samples collected after administration of monoclonal antibodies were excluded. Proportions were compared with McNemar; 3 months after the second and third dose p = 0.248 and 1 month after the third and fourth dose p = 0.480. The number of missing samples in each column (from left to right) were n = 8, n = 9, n = 10, and n = 15, respectively. The missing samples were included in Supplementary Figure 2. RBD, receptor-binding domain.

Figure 2

Anti-spike protein receptor-binding domain IgG antibody levels after different doses of SARS-CoV-2 vaccination and treatment with monoclonal antibodies in individuals with common variable immunodeficiency. The anti-spike receptor-binding domain IgG antibody response after SARS-CoV-2 vaccination (left figures, A and C) and after monoclonal antibody treatment (right figures, B and D). In the left figures, samples collected after administration of monoclonal antibodies were excluded. Data were compared using paired Wilcoxon sign rank tests. Scatters were colored according to immunoglobulin replacement therapy (upper figures, A and B) and COVID-19 (previous vs. naïve) at the time of sampling (lower figures, C and D). One and three months after the third dose and 1 month after the fourth dose, there were no significant variation in spike IgG antibodies across groups of IgRT in Kruskal–Wallis tests (p = 0.881, p = 0.437, and p = 0.460, respectively). RBD, receptor-binding domain; IgRT, immunglobulin replacement therapy. ** p<0.01.