Bacterial extracellular vesicle-coated multi-antigenic nanovaccines protect against drug-resistant Staphylococcus aureus infection by modulating antigen processing and presentation pathways
Bacterial extracellular vesicle-coated multi-antigenic nanovaccines protect against drug-resistant Staphylococcus aureus infection by modulating antigen processing and presentation pathways
复制标题
细菌细胞外囊泡包被的多抗原纳米疫苗通过调节抗原加工和呈递途径来防止耐药金黄色葡萄球菌感染
DOI：
10.7150/thno.44564
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发表时间：
2020-01-01
期刊：
影响因子：
12.4
通讯作者：
Zhou, Xin
中科院分区：
文献类型：
--
作者：
Gang, Chen;Bai, Yanan;Zhou, Xin
背景：疫苗接种为解决耐药金黄色葡萄球菌（金黄色葡萄球菌）感染提供了一种替代抗生素的方法。然而，由于缺乏抗原广度和仅要求产生抗体反应，疫苗效力往往受到限制。方法：利用细菌胞外囊泡（EV）包被吲哚菁绿（ICG）负载的磁性介孔二氧化硅纳米颗粒（MSN）构建多抗原疫苗（EV/ICG/MSN），该疫苗具有调节树突状细胞（DCs）抗原递呈途径以诱导细胞免疫应答的能力。结果：激光照射EV/ICG/ msn可通过促进内溶酶体逃逸、提高蛋白酶体活性和提高MHC-I表达，促进DC成熟，增强蛋白酶体依赖抗原递呈途径。EV/ICG/MSNs在体内激光照射下免疫可改善CD8+ T细胞应答，同时维持CD4+ T细胞应答和体液免疫。此外，体内跟踪数据显示，疫苗可以有效地从注射部位运输到淋巴结。皮肤感染实验表明，该疫苗不仅可以预防和治疗浅表感染，还可以降低细菌的侵袭性，从而强烈提示EV/ICG/MSNs可有效预防金黄色葡萄球菌感染引入引起的并发症。结论：这种以多抗原纳米疫苗为基础的抗原呈递途径调节提供了对抗耐药金黄色葡萄球菌感染的有效策略。
Background: Vaccination provides an alternative to antibiotics in addressing drug-resistant Staphylococcus aureus (S. aureus) infection. However, vaccine potency is often limited by a lack of antigenic breadth and a demand on the generation of antibody responses alone. Methods: In this study, bacterial extracellular vesicles (EVs) coating indocyanine green (ICG)-loaded magnetic mesoporous silica nanoparticles (MSN) were constructed as multi-antigenic vaccines (EV/ICG/MSN) with the ability to modulate antigen presentation pathways in dendritic cells (DCs) to induce cellular immune responses. Results: Exposing the EV/ICG/MSNs to a laser could promote DC maturation and enhance the proteasome-dependent antigen presentation pathway by facilitating endolysosomal escape, improving proteasome activity, and elevating MHC-I expression. Immunization by EV/ICG/MSNs with laser irradiation in vivo triggered improved CD8+ T cell responses while maintaining CD4+ T cell responses and humoral immunity. In addition, in vivo tracking data revealed that the vaccine could be efficiently transported from the injection site into lymph nodes. Skin infection experiments showed that the vaccine not only prevented and treated superficial infection but also decreased bacterial invasiveness, thus strongly suggesting that EV/ICG/MSNs were effective in preventing complications resulting from the introduction of S. aureus infections. Conclusion: This multi-antigenic nanovaccine-based modulation of antigen presentation pathways provides an effective strategy against drug-resistant S. aureus infection.