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IF 14.3 1区医学 Q1 INFECTIOUS DISEASES

Journal of Infection Pub Date : 2025-03-18 DOI:10.1016/j.jinf.2025.106473

Carla Martín Pérez, Sílvia Ruiz-Rius, Anna Ramírez-Morros, Marta Vidal, D Herbert Opi, Pere Santamaria, Julià Blanco, Josep Vidal-Alaball, James G Beeson, Luis M Molinos-Albert, Ruth Aguilar, Anna Ruiz-Comellas, Gemma Moncunill, Carlota Dobaño

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引用次数: 0

摘要

目的重复接种COVID-19 mRNA疫苗会增加SARS-CoV-2 IgG4抗体，这表明在接种第一针加强剂量后IgG亚类发生了广泛的转换。由于 IgG4 介导 Fc 依赖性效应器功能的能力有限，IgG 亚类的这种转变令人担忧：为了评估 IgG4 诱导对保护性免疫的影响，我们分析了西班牙一批特征明确的医护人员的纵向 SARS-CoV-2 IgG 亚类、C1q 和 FcγR 反应以及中和活性：加强免疫后 IgG4 水平升高和非嗜细胞抗体与嗜细胞抗体比率升高与突破性感染风险增加有显著相关性（IgG4 HR[10 倍增长]=1.8，95% CI=1.2-2.7；非嗜细胞抗体与嗜细胞抗体比率 HR[10 倍增长]=1.5，95% CI=1.1-1.9）。此外，非嗜细胞抗体与嗜细胞抗体比率的增加与包括中和在内的功能降低有关：这些研究结果表明，mRNA 疫苗接种诱导 IgG4 与更高的突破性感染风险之间存在潜在联系，因此有必要进一步研究疫苗接种策略，以确保持续的保护。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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Post-vaccination IgG4 and IgG2 class switch associates with increased risk of SARS-CoV-2 infections.

Objectives: Repeated COVID-19 mRNA vaccinations increase SARS-CoV-2 IgG4 antibodies, indicating extensive IgG class switching following the first booster dose. This shift in IgG subclasses raises concerns due to the limited ability of IgG4 to mediate Fc-dependent effector functions.

Methods: To assess the impact of IgG4 induction on protective immunity, we analyzed longitudinal SARS-CoV-2 IgG subclasses, C1q and FcγR responses, and neutralizing activity in a well-characterized cohort of healthcare workers in Spain.

Results: Elevated IgG4 levels and higher ratios of non-cytophilic to cytophilic antibodies after booster vaccination were significantly associated with an increased risk of breakthrough infections (IgG4 HR[10-fold increase]=1.8, 95% CI=1.2-2.7; non-cytophilic to cytophilic ratio HR[10-fold increase]=1.5, 95% CI=1.1-1.9). Moreover, an increased non-cytophilic to cytophilic antibody ratio correlated with reduced functionality, including neutralization.

Conclusions: These findings suggest a potential association between IgG4 induction by mRNA vaccination and a higher risk of breakthrough infection, warranting further investigation into vaccination strategies to ensure sustained protection.

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来源期刊

Journal of Infection 医学-传染病学

CiteScore

45.90

自引率

3.20%

发文量

475

审稿时长

16 days

期刊介绍： The Journal of Infection publishes original papers on all aspects of infection - clinical, microbiological and epidemiological. The Journal seeks to bring together knowledge from all specialties involved in infection research and clinical practice, and present the best work in the ever-changing field of infection. Each issue brings you Editorials that describe current or controversial topics of interest, high quality Reviews to keep you in touch with the latest developments in specific fields of interest, an Epidemiology section reporting studies in the hospital and the general community, and a lively correspondence section.