A multiantigenic antibacterial nanovaccine utilizing hybrid membrane vesicles for combating Pseudomonas aeruginosa infections

IF 15.5 1区 医学 Q1 CELL BIOLOGY
Xinran Peng, Yuanjing Luo, Li Yang, Yi Yan Yang, Peiyan Yuan, Xinhai Chen, Guo-Bao Tian, Xin Ding
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Abstract

Bacterial infections, especially those caused by multidrug-resistant pathogens, pose a significant threat to public health. Vaccines are a crucial tool in fighting these infections; however, no clinically available vaccine exists for the most common bacterial infections, such as those caused by Pseudomonas aeruginosa. Herein, a multiantigenic antibacterial nanovaccine (AuNP@HMV@SPs) is reported to combat P. aeruginosa infections. This nanovaccine utilizes the hybrid membrane vesicles (HMVs) created by fusing macrophage membrane vesicles (MMVs) with bacterial outer membrane vesicles (OMVs). The HMVs mitigate the toxic effects of both OMVs and bacterial secreted toxins (SP) adsorbed on the surface of MMVs, while preserving their stimulating properties. Gold nanoparticles (AuNPs) are utilized as adjuvant to enhance immune response without comprising safety. The nanovaccine AuNP@HMV@SPs induces robust humoral and cellular immune responses, leading to destruction of bacterial cells and neutralization of their secreted toxins. In murine models of septicemia and pneumonia caused by P. aeruginosa, AuNP@HMV@SPs exhibits superior prophylactic efficacy compared to control groups including OMVs, or MMVs@SPs and HMV@SPs, achieving 100% survival in septicemia and > 99.9% reduction in lung bacterial load in pneumonia. This study highlights AuNP@HMV@SPs as a safe and effective antibacterial nanovaccine, targeting both bacteria and their secreted toxins, and offers a promising platform for developing multiantigenic antibacterial vaccines against multidrug-resistant pathogens.

Abstract Image

利用杂交膜囊泡抗铜绿假单胞菌感染的多抗原抗菌纳米疫苗
细菌感染,尤其是由耐多药病原体引起的细菌感染,对公共卫生构成了严重威胁。疫苗是抗击这些感染的重要工具;然而,对于最常见的细菌感染,如铜绿假单胞菌引起的感染,目前还没有临床可用的疫苗。本文报告了一种多抗原抗菌纳米疫苗(AuNP@HMV@SPs),用于抗击铜绿假单胞菌感染。这种纳米疫苗利用了巨噬细胞膜囊泡与细菌外膜囊泡融合产生的杂交膜囊泡(HMVs)。HMVs 可减轻 OMVs 和吸附在 MMVs 表面的细菌分泌毒素 (SP) 的毒性作用,同时保留其刺激特性。金纳米粒子(AuNPs)可用作佐剂,在不影响安全性的情况下增强免疫反应。纳米疫苗 AuNP@HMV@SPs 可诱导强有力的体液和细胞免疫反应,从而破坏细菌细胞并中和其分泌的毒素。在铜绿假单胞菌引起的小鼠败血症和肺炎模型中,AuNP@HMV@SPs 与包括 OMVs 或 MMVs@SPs 和 HMV@SPs 在内的对照组相比,显示出更优越的预防效果,败血症患者存活率达到 100%,肺炎患者肺部细菌量减少 99.9%。这项研究表明,AuNP@HMV@SPs 是一种安全有效的抗菌纳米疫苗,可同时针对细菌及其分泌的毒素,为开发针对耐多药病原体的多抗原抗菌疫苗提供了一个前景广阔的平台。
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来源期刊
Journal of Extracellular Vesicles
Journal of Extracellular Vesicles Biochemistry, Genetics and Molecular Biology-Cell Biology
CiteScore
27.30
自引率
4.40%
发文量
115
审稿时长
12 weeks
期刊介绍: The Journal of Extracellular Vesicles is an open access research publication that focuses on extracellular vesicles, including microvesicles, exosomes, ectosomes, and apoptotic bodies. It serves as the official journal of the International Society for Extracellular Vesicles and aims to facilitate the exchange of data, ideas, and information pertaining to the chemistry, biology, and applications of extracellular vesicles. The journal covers various aspects such as the cellular and molecular mechanisms of extracellular vesicles biogenesis, technological advancements in their isolation, quantification, and characterization, the role and function of extracellular vesicles in biology, stem cell-derived extracellular vesicles and their biology, as well as the application of extracellular vesicles for pharmacological, immunological, or genetic therapies. The Journal of Extracellular Vesicles is widely recognized and indexed by numerous services, including Biological Abstracts, BIOSIS Previews, Chemical Abstracts Service (CAS), Current Contents/Life Sciences, Directory of Open Access Journals (DOAJ), Journal Citation Reports/Science Edition, Google Scholar, ProQuest Natural Science Collection, ProQuest SciTech Collection, SciTech Premium Collection, PubMed Central/PubMed, Science Citation Index Expanded, ScienceOpen, and Scopus.
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