Humoral response to mRNA vaccines against SARS-CoV-2 in patients with humoral immunodeficiency disease

Abstract

Objectives: Although mRNA-based vaccines against SARS-CoV-2 induce a robust immune response and prevent infections and hospitalizations, there are limited data on the antibody response in individuals with humoral immunodeficiency. The aim of this study was to evaluate the humoral immune response after two vaccine doses with BNT162b2 or mRNA-1273 in patients with humoral immunodeficiency disease.

Methods: This cross-sectional study assessed 39 individuals with hypogammaglobulinemia under immunoglobulin replacement therapy. IgG anti-SARS-CoV-2 spike protein antibodies (anti-S) were measured 4 weeks to 4 months after two doses of an mRNA vaccine against SARS-CoV-2. The proportion of patients, who developed a humoral immune response to the spike protein were evaluated and compared to 19 healthy controls.

Results: After vaccination with two vaccine doses, 26/39 patients (66.7%) with humoral immunodeficiency disease and all healthy controls developed anti-S. In subjects with baseline IgG <3 g/l, only 1/5 (20%) showed a humoral immune response. 10 out of 26 with CVID (38.5%) and 7/9 under immunosuppressive drugs (77.8%) developed no immune response (13 subjects with no response) compared to 0/19 in healthy controls. Subgroup analysis in patients without immunosuppressive drugs revealed lower anti-S in patients with moderate to severe humoral immunodeficiency disease: baseline IgG <3 g/l: 12.0 AU/ml (95%CI 12.0-125.0), baseline IgG 3-5 g/l: 99.9 AU/ml (95%CI 14.4-400.0), baseline IgG >5 g/l: 151.5 AU/ml (95%CI 109.0-400.0), healthy controls 250.0 AU/ml (95%CI 209.0-358.0), p = 0.007.

Conclusion: In most patients with mild to moderate humoral immunodeficiency we found only slightly lower anti-S antibodies compared with healthy controls after two vaccine doses with BNT162b2 and mRNA-1273. However, in patients with a decreased baseline IgG below 3 g/l and/or under immunosuppressive drugs, we found severely impaired humoral immune responses.

Fig 1. Proportion of patients with anti-S after two Covid-19 mRNA doses.

Proportion of patients with humoral immune response to SARS-CoV-2 spike protein (anti-S) are shown in total and for various subgroups (Anti-SARS-CoV-2 spike protein antibodies cutoff >12 AU/ml). Baseline IgG values indicate the severity of the humoral immunodeficiency disease at start of immunoglobulin replacement therapy. P values are calculated by Chi-square test. Anti-SARS-CoV-2 spike protein antibodies (anti-S).

Fig 2. Anti-S quantity subgroup analysis.

All included patients were divided into subgroups according to baseline total IgG levels at start of immunoglobulin replacement therapy. Kruskal-Wallis test was calculated for the comparison of the IgG subgroups and healthy control: p = 0.002. Anti-SARS-CoV-2 spike protein antibodies (anti-S).

Fig 3. Anti-S quantity after 3. vaccination.

Data of SARS-CoV-2-IgG spike protein values of 22 patients with a third mRNA vaccination, including 7 persons under immunosuppressive drugs. In the two subjects with decreasing SARS-CoV-2-IgG spike protein levels despite third vaccination, laboratory analysis was not performed until 4 months after the third vaccination. Subjects under immunosuppressive treatment are marked with square. The p value was calculated by Mann-Whitney test.