在常见变异性免疫缺陷个体中，第三和第四剂 SARS-CoV-2 疫苗后的抗体反应。

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

机构信息

Department of Infectious Diseases, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.

Department of Clinical Immunology, Odense University Hospital, Odense, Denmark.

出版信息

Front Immunol. 2022 Jul 28;13:934476. doi: 10.3389/fimmu.2022.934476. eCollection 2022.

DOI:10.3389/fimmu.2022.934476

PMID:35967433

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9366053/

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], = 0.006) and tended to increase after the fourth dose (193 BAU/ml, [-22; 569 BAU/ml], = 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 ( = 0.009). IgRT products had varying concentrations of anti-S-RBD ( < 0.001), but none of the products seemed to affect the overall antibody levels ( = 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.

摘要

背景

在常见变异性免疫缺陷（CVID）中，疫苗接种后的抗体反应受损。

目的

我们旨在研究四剂 SARS-CoV-2 疫苗接种策略和 CVID 中单克隆抗体（mAB）治疗后刺突受体结合域 IgG 抗体（抗-S-RBD）水平。此外，我们评估了免疫球蛋白替代疗法（IgRT）产品中的抗-S-RBD 水平。

方法

在一项观察性研究中，我们检查了 mRNA SARS-CoV-2 疫苗第二、第三和第四剂后的抗-S-RBD 水平。此外，我们还测量了 mAB 治疗后的抗-S-RBD。最后，评估了常见 IgRT 产品中的抗-S-RBD。通过 McNemar 检验比较抗体无应答者（抗-S-RBD < 7.1），并通过配对和非配对 Wilcoxon 符号秩检验以及 Kruskal-Wallis 检验比较抗-S-RBD 水平。

结果

在 33 名 CVID 患者中，第三剂疫苗后抗-S-RBD 水平升高（165 BAU/ml [95%置信区间：85；2280 BAU/ml]， = 0.006），第四剂疫苗后抗-S-RBD 水平有升高趋势（193 BAU/ml，[-22；569 BAU/ml]， = 0.080）。随着接种次数的增加，血清转换患者（抗-S-RBD≥7.1）的比例无显著增加。mAB 治疗导致抗-S-RBD 大幅增加，且高于第四剂疫苗后的中位数水平（ = 0.009）。IgRT 产品具有不同浓度的抗-S-RBD（ < 0.001），但没有一种产品似乎影响总体抗体水平（ = 0.460）。