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Safe Staphylococcal Platform for the Development of Multivalent Nanoscale Vesicles against Viral Infections
Nano Letters ( IF 9.6 ) Pub Date : 2018-01-05 00:00:00 , DOI: 10.1021/acs.nanolett.7b03893 Jizhen Yuan 1 , Jie Yang 1 , Zhen Hu 1 , Yi Yang 1 , Weilong Shang 1 , Qiwen Hu 1 , Ying Zheng 1 , Huagang Peng 1 , Xiaopeng Zhang 1 , Xinyu Cai 2 , Junmin Zhu 1 , Ming Li 1 , Xiaomei Hu 1 , Renjie Zhou 2 , Xiancai Rao 1
Nano Letters ( IF 9.6 ) Pub Date : 2018-01-05 00:00:00 , DOI: 10.1021/acs.nanolett.7b03893 Jizhen Yuan 1 , Jie Yang 1 , Zhen Hu 1 , Yi Yang 1 , Weilong Shang 1 , Qiwen Hu 1 , Ying Zheng 1 , Huagang Peng 1 , Xiaopeng Zhang 1 , Xinyu Cai 2 , Junmin Zhu 1 , Ming Li 1 , Xiaomei Hu 1 , Renjie Zhou 2 , Xiancai Rao 1
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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 (ΔagrMVs) 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 ΔagrMVs. The presentation levels were (3.43 ± 0.73)%, (5.07 ± 0.82)%, (2.64 ± 0.61)%, and (2.89 ± 0.74)% of the total ΔagrMV 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 ΔagrMVs. Administration of such engineered ΔagrMVs 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.
中文翻译：
安全的葡萄球菌平台，用于开发抗病毒感染的多价纳米囊泡。
许多病毒通常具有密切相关但在抗原上不同的血清型。理想的抗病毒感染疫苗应诱导针对所有血清型的多价保护性免疫应答。受携带不同蛋白质成分的细菌膜囊泡（MVs）的启发，我们构建了金黄色葡萄球菌菌株（RN4220-Δagr）的agr基因座缺失突变体，以减少潜在的毒性。来源于该菌株的纳米囊泡（ΔagrMVs）带有至少四个主要成分，可以传递异源抗原。这些组件分别与三重FLAG标签融合，并且可以将已标记的蛋白掺入Δagr中MV。呈递水平为Mntc-FLAG，PdhB-FLAG，PdhA-FLAG的总ΔagrMV蛋白的（3.43±0.73）％，（5.07±0.82）％，（2.64±0.61）％和（2.89±0.74）％，和Eno-FLAG。以两个DENV包膜E结构域III蛋白（EDIIIconA和EDIIIconB）为模型，由两个葡萄球菌成分递送的DENV EDIIIconA和EDIIIconB被稳定地包埋在ΔagrMVs中。在小鼠中施用这种工程改造的ΔagrMVs诱导针对所有四种DENV血清型的抗体。免疫小鼠的血清可保护Vero细胞和乳鼠免受DENV-2的致死性攻击。这项研究将为制备针对病毒感染的多价纳米级病毒疫苗开辟新的见解。
更新日期：2018-01-05
中文翻译：
安全的葡萄球菌平台，用于开发抗病毒感染的多价纳米囊泡。
许多病毒通常具有密切相关但在抗原上不同的血清型。理想的抗病毒感染疫苗应诱导针对所有血清型的多价保护性免疫应答。受携带不同蛋白质成分的细菌膜囊泡（MVs）的启发，我们构建了金黄色葡萄球菌菌株（RN4220-Δagr）的agr基因座缺失突变体，以减少潜在的毒性。来源于该菌株的纳米囊泡（ΔagrMVs）带有至少四个主要成分，可以传递异源抗原。这些组件分别与三重FLAG标签融合，并且可以将已标记的蛋白掺入Δagr中MV。呈递水平为Mntc-FLAG，PdhB-FLAG，PdhA-FLAG的总ΔagrMV蛋白的（3.43±0.73）％，（5.07±0.82）％，（2.64±0.61）％和（2.89±0.74）％，和Eno-FLAG。以两个DENV包膜E结构域III蛋白（EDIIIconA和EDIIIconB）为模型，由两个葡萄球菌成分递送的DENV EDIIIconA和EDIIIconB被稳定地包埋在ΔagrMVs中。在小鼠中施用这种工程改造的ΔagrMVs诱导针对所有四种DENV血清型的抗体。免疫小鼠的血清可保护Vero细胞和乳鼠免受DENV-2的致死性攻击。这项研究将为制备针对病毒感染的多价纳米级病毒疫苗开辟新的见解。
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