Enhanced T-cell immunity and lower humoral responses following 5-dose SARS-CoV-2 vaccination in patients with inborn errors of immunity compared with healthy controls.

IF 5.7 2区医学 Q1 IMMUNOLOGY

Frontiers in Immunology Pub Date : 2025-03-06 eCollection Date: 2025-01-01 DOI:10.3389/fimmu.2025.1538453

Vitor Gabriel Lopes da Silva, Gabriela Justamante Händel Schmitz, Kathleen E Sullivan, Júlia Barbate, Maria Izabel de Haro Azinar, Carolina Sanchez Aranda, Maria Isabel de Moraes-Pinto

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Abstract

Objective: Patients with Inborn Errors of Immunity (IEI) are at higher risk of severe SARS-CoV-2 infection. We evaluated humoral and cellular responses to COVID-19 vaccines in Brazilian patients with IEI and healthy controls.

Methods: Fifty-five patients with IEI (13-61 years) and 60 controls (13-71 years) received inactivated SARS-CoV-2 (CoronaVac), non-replicating virus-vectored (ChAdOx1 nCoV-19, AstraZeneca) or monovalent mRNA (Original strain of BNT162b2, Pfizer-BioNTech) and bivalent mRNA (Original/Omicron BA.1, Pfizer-BioNTech) vaccines and were sampled five times. Diagnoses included common variable immunodeficiency (n=25), specific antibody deficiency (n=9), ataxia-telangiectasia (n=5), X-linked agammaglobulinemia (n=4), PIK3CD-related disorders (n=4), hyper-IgM syndrome (n=4), combined immunodeficiency (n=3), and STAT1 gain-of-function (n=1). Humoral immunity was assessed via multiplex microarray for Spike, Nucleocapsid, RBD-Wuhan, RBD-Delta, RBD-BA.1, RBD-BA.2 and RBD-BA.5 neutralizing antibodies. T-cell responses to Spike and Nucleocapsid were assessed using ELISpot.

Results: Patients with IEI exhibited significantly lower levels of Nucleocapsid and RBD-neutralizing antibodies (p < 0.05). Notable differences in RBD-BA.2 (p = 0.008) and IgG-Nucleocapsid (p = 0.010) levels emerged over time. T-cell responses to Spike were stronger in patients with IEI post-booster (405 vs. 149 spot-forming cells/million PBMC; p = 0.002). Both groups showed enhanced Nucleocapsid-specific cellular responses over time (p = 0.017). COVID-19 hospitalization rates among patients with IEI with SARS-CoV-2 diagnosis dropped from 33.3% to zero after the first booster dose.

Conclusions: While humoral responses to SARS-CoV-2 vaccines were weaker in patients with IEI, their cellular immunity was similar to controls. Boosters enhanced both humoral and cellular responses. After completion of the vaccination protocol, none of the patients with IEI were hospitalized with COVID-19. Robust T-cell responses may play a critical role in protecting patients with IEI from severe COVID-19 and mortality.

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与健康对照组相比，先天性免疫错误患者接种 5 剂 SARS-CoV-2 疫苗后 T 细胞免疫力增强，体液免疫力下降。

目的先天性免疫错误（IEI）患者感染严重 SARS-CoV-2 的风险较高。我们评估了巴西 IEI 患者和健康对照组对 COVID-19 疫苗的体液和细胞反应：55 名 IEI 患者（13-61 岁）和 60 名对照组患者（13-71 岁）接种了灭活 SARS-CoV-2 疫苗（CoronaVac）、非复制病毒载体疫苗（ChAdOx1 nCoV-19，阿斯利康）或单价 mRNA 疫苗（BNT162b2 原始株，辉瑞生物技术公司）和双价 mRNA 疫苗（Original/Omicron BA.1，辉瑞生物技术公司），并进行了 5 次采样。诊断包括常见变异性免疫缺陷（25 例）、特异性抗体缺乏（9 例）、共济失调-特朗日病（5 例）、X 连锁丙种球蛋白血症（4 例）、PIK3CD 相关疾病（4 例）、高 IgM 综合征（4 例）、联合免疫缺陷（3 例）和 STAT1 功能获得（1 例）。体液免疫通过多重微阵列评估斯派克、核头、RBD-武汉、RBD-Delta、RBD-BA.1、RBD-BA.2和RBD-BA.5中和抗体。使用 ELISpot 评估对 Spike 和 Nucleocapsid 的 T 细胞反应：结果：IEI患者的核头壳和RBD中和抗体水平明显较低（p < 0.05）。随着时间的推移，RBD-BA.2（p = 0.008）和IgG-Nucleocapsid（p = 0.010）水平出现明显差异。IEI患者在强化后对 Spike 的 T 细胞反应更强（405 个形成斑点的细胞/百万 PBMC 与 149 个形成斑点的细胞/百万 PBMC；p = 0.002）。随着时间的推移，两组患者的核苷酸特异性细胞反应均有所增强（p = 0.017）。确诊为SARS-CoV-2的IEI患者的COVID-19住院率在首次加强剂量后从33.3%降至零：结论：虽然 IEI 患者对 SARS-CoV-2 疫苗的体液免疫反应较弱，但他们的细胞免疫与对照组相似。加强剂增强了体液和细胞反应。完成疫苗接种后，没有一名 IEI 患者因 COVID-19 而住院。强大的 T 细胞应答可能在保护 IEI 患者免受严重 COVID-19 感染和避免死亡方面发挥着关键作用。

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来源期刊

Frontiers in Immunology IMMUNOLOGY-

CiteScore

9.80

自引率

11.00%

发文量

7153

审稿时长

14 weeks

期刊介绍： Frontiers in Immunology is a leading journal in its field, publishing rigorously peer-reviewed research across basic, translational and clinical immunology. This multidisciplinary open-access journal is at the forefront of disseminating and communicating scientific knowledge and impactful discoveries to researchers, academics, clinicians and the public worldwide. Frontiers in Immunology is the official Journal of the International Union of Immunological Societies (IUIS). Encompassing the entire field of Immunology, this journal welcomes papers that investigate basic mechanisms of immune system development and function, with a particular emphasis given to the description of the clinical and immunological phenotype of human immune disorders, and on the definition of their molecular basis.