A universal vaccine design platform that can rapidly generate multiplex vaccine candidates is critically needed to control future pandemics. Here, using SARS-CoV-2 pandemic virus as a model, we have developed such a platform by CRISPR engineering of bacteriophage T4. A pipeline of vaccine candidates were engineered by incorporating various viral components into appropriate compartments of phage nanoparticle structure. These include: expressible spike genes in genome, spike and envelope epitopes as surface decorations, and nucleocapsid proteins in packaged core. Phage decorated with spike trimers is found to be the most potent vaccine candidate in mouse and rabbit models. Without any adjuvant, this vaccine stimulated robust immune responses, both TH1 and TH2 IgG subclasses, blocked virus-receptor interactions, neutralized viral infection, and conferred complete protection against viral challenge. This new type of nanovaccine design framework might allow rapid deployment of effective phage-based vaccines against any emerging pathogen in the future.

中文翻译：

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通过 CRISPR 工程设计多重 SARS-CoV-2 候选疫苗的通用噬菌体 T4 纳米颗粒平台

迫切需要一个能够快速生成多重候选疫苗的通用疫苗设计平台来控制未来的大流行。在这里，我们以 SARS-CoV-2 大流行病毒为模型，通过噬菌体 T4 的 CRISPR 工程开发了这样一个平台。通过将各种病毒成分整合到噬菌体纳米颗粒结构的适当隔室中，设计了一系列候选疫苗。这些包括：基因组中可表达的刺突基因，作为表面装饰的刺突和包膜表位，以及包装核心中的核衣壳蛋白。发现用刺突三聚体修饰的噬菌体是小鼠和兔模型中最有效的候选疫苗。在没有任何佐剂的情况下，这种疫苗刺激了强大的免疫反应，包括 TH1 和 TH2 IgG 亚类，阻断病毒-受体相互作用，中和病毒感染，并赋予对病毒攻击的完全保护。这种新型纳米疫苗设计框架可能允许在未来快速部署有效的基于噬菌体的疫苗来对抗任何新出现的病原体。