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 AB₅ toxin and unnatural trimer peptides, diverse nanovaccine structures can be produced in common Escherichia coli strains 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.

中文翻译：

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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。

近年来，在预防性和治疗性应用方面，纳米疫苗取得了巨大的进步，但是这些技术中的大多数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仅生物学过程，例如复杂的顺序翻译后生化修饰和可扩展性，限制了实现与传统疫苗相比具有重大性能优势和改善治疗效果的最初承诺。本文介绍了一个Nano-B5平台，可在体内生产完全基于蛋白质的，自组装的，稳定的纳米疫苗，该疫苗带有多种抗原，包括肽和多糖。结合细菌AB ₅的五聚体结构域的自组装能力毒素和非天然三聚体肽，可以在常见的大肠杆菌菌株和减毒的致病菌株中产生多种纳米疫苗结构。值得注意的是，这些纳米疫苗的底物起免疫刺激剂的作用。在小鼠和猴子模型中均显示出优异的淋巴结靶向性，免疫应答诱发性和安全性后，这些纳米疫苗对感染的强力预防作用以及对肿瘤的有效治疗作用得到了进一步证明。因此，Nano-B5平台可以有效地结合各种模块化组件和抗原货物，从而利用许多细菌物种有效地产生可能非常庞大的纳米疫苗结构。