Extracellular Vesicles are Key Mediators for Direct Antigen Transport to Draining Lymph Nodes.

IF 12 1区医学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Molecular Therapy Pub Date : 2025-10-16 DOI:10.1016/j.ymthe.2025.10.034

Chunxi Wang,Xiao Cheng,Ke Cheng,Fan Yuan

{"title":"Extracellular Vesicles are Key Mediators for Direct Antigen Transport to Draining Lymph Nodes.","authors":"Chunxi Wang,Xiao Cheng,Ke Cheng,Fan Yuan","doi":"10.1016/j.ymthe.2025.10.034","DOIUrl":null,"url":null,"abstract":"DNA vaccines have shown great potential in preclinical and clinical studies. However, it is still unclear how the antigen expressed at the site of vaccination is delivered to draining lymph nodes for activation of the immune system. To address the issue, the current study investigated the role of extracellular vesicles (EVs) in the delivery. Following intramuscular electrotransfection of DNA vaccines encoding a transmembrane antigen, hemagglutinin (HA), EV secretion was significantly increased in the muscle with the peak level being ∼10-fold higher than the unvaccinated control. More importantly, the EVs were highly enriched with HA, and could reach the draining lymph nodes through lymphatic vessels within 4 hours. Blocking the EV secretion by systemic treatment with a small molecular inhibitor, GW4869, significantly reduced humoral and cellular responses against the antigen. These findings indicated that the EVs play an important role in the antigen delivery, suggesting that enhancing local EV biogenesis and antigen packaging into EVs can be new avenues for development of next generation vaccine adjuvants.","PeriodicalId":19020,"journal":{"name":"Molecular Therapy","volume":"104 1","pages":""},"PeriodicalIF":12.0000,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Molecular Therapy","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.ymthe.2025.10.034","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOTECHNOLOGY & APPLIED MICROBIOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

DNA vaccines have shown great potential in preclinical and clinical studies. However, it is still unclear how the antigen expressed at the site of vaccination is delivered to draining lymph nodes for activation of the immune system. To address the issue, the current study investigated the role of extracellular vesicles (EVs) in the delivery. Following intramuscular electrotransfection of DNA vaccines encoding a transmembrane antigen, hemagglutinin (HA), EV secretion was significantly increased in the muscle with the peak level being ∼10-fold higher than the unvaccinated control. More importantly, the EVs were highly enriched with HA, and could reach the draining lymph nodes through lymphatic vessels within 4 hours. Blocking the EV secretion by systemic treatment with a small molecular inhibitor, GW4869, significantly reduced humoral and cellular responses against the antigen. These findings indicated that the EVs play an important role in the antigen delivery, suggesting that enhancing local EV biogenesis and antigen packaging into EVs can be new avenues for development of next generation vaccine adjuvants.

查看原文本刊更多论文

细胞外囊泡是抗原直接转运到引流淋巴结的关键介质。

DNA疫苗在临床前和临床研究中显示出巨大的潜力。然而，目前尚不清楚在接种部位表达的抗原如何被递送到引流淋巴结以激活免疫系统。为了解决这个问题，目前的研究调查了细胞外囊泡（EVs）在分娩中的作用。在肌肉内电转染编码跨膜抗原血凝素（HA）的DNA疫苗后，肌肉中EV的分泌显著增加，峰值水平比未接种疫苗的对照组高约10倍。更重要的是，ev富含HA，并能在4小时内通过淋巴管到达引流淋巴结。用小分子抑制剂GW4869全身阻断EV分泌，可显著降低体液和细胞对抗原的反应。这些研究结果表明，EV在抗原递送中发挥着重要作用，加强EV的局部生物发生和抗原包装可能是开发下一代疫苗佐剂的新途径。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Molecular Therapy 医学-生物工程与应用微生物

CiteScore

19.20

自引率

3.20%

发文量

357

审稿时长

3 months

期刊介绍： Molecular Therapy is the leading journal for research in gene transfer, vector development, stem cell manipulation, and therapeutic interventions. It covers a broad spectrum of topics including genetic and acquired disease correction, vaccine development, pre-clinical validation, safety/efficacy studies, and clinical trials. With a focus on advancing genetics, medicine, and biotechnology, Molecular Therapy publishes peer-reviewed research, reviews, and commentaries to showcase the latest advancements in the field. With an impressive impact factor of 12.4 in 2022, it continues to attract top-tier contributions.