Safe Staphylococcal Platform for the Development of Multivalent Nanoscale Vesicles against Viral Infections

作者：Jizhen Yuan, Jie Yang, Zhen Hu, Yi Yang, Weilong Shang, Qiwen Hu, Ying Zheng, Huagang Peng, Xiaopeng Zhang, Xinyu Cai, Junmin Zhu, Ming Li, Xiaomei Hu, Renjie Zhou, Xiancai Rao · 发表于：Nano Letters · 年份：2017 · DOI：10.1021/acs.nanolett.7b03893 · 被引用次数：53 · 研究领域：Bacterial Infections and Vaccines、Viral Infections and Immunology Research、Bacteriophages and microbial interactions

High Resolution Image Download MS PowerPoint Slide Many viruses often have closely related yet antigenically distinct serotypes. An ideal vaccine against viral infections should induce a multivalent and protective immune response against all serotypes. Inspired by bacterial membrane vesicles (MVs) that carry different protein components, we constructed an agr locus deletion mutant of the Staphylococcus aureus strain (RN4220-Δagr) to reduce potential toxicity. Nanoscale vesicles derived from this strain ( Δagr MVs) carry at least four major components that can deliver heterologous antigens. These components were each fused with a triple FLAG tag, and the tagged proteins could be incorporated into the Δagr MVs. The presentation levels were (3.43 ± 0.73)%, (5.07 ± 0.82)%, (2.64 ± 0.61)%, and (2.89 ± 0.74)% of the total Δagr MV proteins for Mntc-FLAG, PdhB-FLAG, PdhA-FLAG, and Eno-FLAG, respectively. With two DENV envelope E domain III proteins (EDIIIconA and EDIIIconB) as models, the DENV EDIIIconA and EDIIIconB delivered by two staphylococcal components were stably embedded in the Δagr MVs. Administration of such engineered Δagr MVs in mice induced antibodies against all four DENV serotypes. Sera from immunized mice protected Vero cells and suckling mice from a lethal challenge of DENV-2. This study will open up new insights into the preparation of multivalent nanosized viral vaccines against viral infections.