Biosynthesis of Self-Assembled Proteinaceous Nanoparticles for Vaccination
Biosynthesis of Self-Assembled Proteinaceous Nanoparticles for Vaccination
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用于疫苗接种的自组装蛋白质纳米颗粒的生物合成
DOI：
10.1002/adma.202002940
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发表时间：
2020-09-02
影响因子：
29.4
通讯作者：
Wang, Hengliang
中科院分区：
文献类型：
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作者：
Pan, Chao;Wu, Jun;Wang, Hengliang
近年来，纳米疫苗在预防和治疗应用方面取得了巨大进展，但这些技术大多采用化学或混合半生物合成生产方法。因此，迄今为止，纳米疫苗的生产未能利用纯生物学过程，如复杂的连续翻译后生化修饰和可扩展性，限制了实现提供主要性能优势和改善传统疫苗治疗效果的最初承诺。本文介绍了一种用于体内生产完全基于蛋白质的、自组装的、稳定的纳米疫苗的Nano-B5平台，该纳米疫苗具有多种抗原，包括肽和多糖。结合细菌AB（5）毒素和非天然三聚体肽的五聚体结构域的自组装能力，可以在常见大肠杆菌菌株和减毒致病菌株中产生不同的纳米疫苗结构。值得注意的是，这些纳米疫苗的底盘起免疫刺激剂的作用。在小鼠和猴模型中显示出优异的淋巴结靶向和免疫应答诱导以及安全性能之后，进一步证明了这些纳米疫苗对感染的强预防作用以及它们对肿瘤的有效治疗作用。因此，Nano-B5平台可以有效地联合收割机组合不同的模块化组分和抗原货物，以使用许多细菌物种有效地产生潜在的非常大的多样性的纳米疫苗结构。
Recent years have seen enormous advances in nanovaccines for both prophylactic and therapeutic applications, but most of these technologies employ chemical or hybrid semi-biosynthetic production methods. Thus, production of nanovaccines has to date failed to exploit biology-only processes like complex sequential post-translational biochemical modifications and scalability, limiting the realization of the initial promise for offering major performance advantages and improved therapeutic outcomes over conventional vaccines. A Nano-B5 platform for in vivo production of fully protein-based, self-assembling, stable nanovaccines bearing diverse antigens including peptides and polysaccharides is presented here. Combined with the self-assembly capacities of pentamer domains from the bacterial AB(5)toxin and unnatural trimer peptides, diverse nanovaccine structures can be produced in commonEscherichia colistrains and in attenuated pathogenic strains. Notably, the chassis of these nanovaccines functions as an immunostimulant. After showing excellent lymph node targeting and immunoresponse elicitation and safety performance in both mouse and monkey models, the strong prophylactic effects of these nanovaccines against infection, as well as their efficient therapeutic effects against tumors are further demonstrated. Thus, the Nano-B5 platform can efficiently combine diverse modular components and antigen cargos to efficiently generate a potentially very large diversity of nanovaccine structures using many bacterial species.