Impact of systemic SARS-CoV-2 vaccination on mucosal IgA responses to subsequent breakthrough infection.

IF 10.8 1区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

EBioMedicine Pub Date : 2025-09-16 DOI:10.1016/j.ebiom.2025.105912

Ulrika Marking, Oscar Bladh, Katherina Aguilera, Tamas Pongracz, Sebastian Havervall, Nina Greilert-Norin, Kim Blom, Jonas Klingström, Yunzhang Wang, Mikael Åberg, Charlotte Thålin

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引用次数: 0

Abstract

Background: Mucosal IgA responses are central to protection against SARS-CoV-2 infection and viral transmission. While systemic immunity following SARS-CoV-2 infection and vaccination is thoroughly investigated, we have limited understanding of factors affecting the generation and boosting of mucosal IgA.

Methods: In this cohort study, we investigated factors influencing mucosal SARS-CoV-2 IgA responses among 879 healthcare workers enrolled in the longitudinal COMMUNITY study. Blood samples and clinical data were collected from all participants every four months since April 2020. SARS-CoV-2 immune histories are well characterized through national vaccine and infection registries along with regular monitoring of seroconversion of spike and/or nucleocapsid antigen. Regression models were developed to assess the influence of vaccinations and prior infections on the magnitude of SARS-CoV-2 spike-specific IgA in nasal secretions collected from the cohort in October 2022.

Findings: Mucosal SARS-CoV-2 spike-specific IgA was detected in 81% of participants, with a positive association with number of prior infections, indicating a booster effect by reinfection. The increased odds ratio of detectable mucosal IgA remained for at least 22 months post infection. There was a strong association between repeated systemic vaccinations and a lower magnitude of mucosal IgA responses. Moreover, the temporal sequence of infection and vaccination influenced mucosal IgA responses, with higher levels among participants with infection prior to systemic vaccination as compared to those with breakthrough infection as the first viral encounter.

Interpretation: The observation that repeated mucosal exposures elicit enhanced and long-lasting mucosal IgA responses strengthens the rationale for developing effective mucosal vaccines. While systemic vaccination remains essential for preventing severe disease, our findings suggest that it may influence subsequent generation of mucosal IgA trough a reduction of viral load and inflammation in the mucosa. This is highly relevant for both understanding the development of population immunity and for optimizing the timing of a sequential systemic and mucosal vaccination approach.

Funding: This study was supported by grants from Region Stockholm, and SciLifeLab and the Knut and Alice Wallenberg Foundation, SSMF and European Research Council. We thank the Public Health Agency of Sweden for support.

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系统性SARS-CoV-2疫苗接种对随后突破性感染的黏膜IgA反应的影响

背景：粘膜IgA反应是防止SARS-CoV-2感染和病毒传播的核心。虽然对SARS-CoV-2感染和疫苗接种后的全身免疫进行了深入研究，但我们对影响粘膜IgA产生和增强的因素的了解有限。方法：在这项队列研究中，我们调查了879名参加COMMUNITY纵向研究的医护人员粘膜SARS-CoV-2 IgA反应的影响因素。自2020年4月以来，每四个月收集一次所有参与者的血液样本和临床数据。通过国家疫苗和感染登记以及对刺突和/或核衣壳抗原血清转化的定期监测，可以很好地描述SARS-CoV-2的免疫史。建立了回归模型，以评估疫苗接种和既往感染对2022年10月收集的队列鼻分泌物中SARS-CoV-2尖峰特异性IgA大小的影响。结果：在81%的参与者中检测到粘膜SARS-CoV-2刺突特异性IgA，与先前感染的数量呈正相关，表明再次感染具有增强作用。可检测到的粘膜IgA的优势比增加在感染后至少持续22个月。反复全身接种疫苗与较低程度的粘膜IgA反应之间存在很强的关联。此外，感染和接种疫苗的时间顺序影响了粘膜IgA反应，在全身接种疫苗之前感染的参与者中，与首次遭遇病毒的突破性感染相比，IgA水平更高。解释：观察到反复的粘膜暴露引起增强和持久的粘膜IgA反应，加强了开发有效粘膜疫苗的理论基础。虽然全身疫苗接种对于预防严重疾病仍然是必不可少的，但我们的研究结果表明，它可能通过减少粘膜中的病毒载量和炎症来影响粘膜IgA的后续产生。这对于理解人群免疫的发展和优化连续全身和粘膜疫苗接种方法的时机都是高度相关的。资金：本研究由斯德哥尔摩地区、sciilifelab、Knut and Alice Wallenberg基金会、SSMF和欧洲研究委员会资助。我们感谢瑞典公共卫生局的支持。

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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来源期刊

EBioMedicine Biochemistry, Genetics and Molecular Biology-General Biochemistry,Genetics and Molecular Biology

CiteScore

17.70

自引率

0.90%

发文量

579

审稿时长

5 weeks

期刊介绍： eBioMedicine is a comprehensive biomedical research journal that covers a wide range of studies that are relevant to human health. Our focus is on original research that explores the fundamental factors influencing human health and disease, including the discovery of new therapeutic targets and treatments, the identification of biomarkers and diagnostic tools, and the investigation and modification of disease pathways and mechanisms. We welcome studies from any biomedical discipline that contribute to our understanding of disease and aim to improve human health.