The major histocompatibility complex class I (MHCI) trafficking signal (MITD) plays a pivotal role in enhancing the efficacy of mRNA vaccines. However, there was a lack of research investigating its efficacy in enhancing immune responses to RNA virus infections. Here, we have developed an innovative strategy for the formulation of mRNA vaccines. This approach involved the integration of MITD into the mRNA sequence encoding the virus antigen. Mechanistically, MITD‐based mRNA vaccines can strengthen immune protection by mimicking the dynamic trafficking properties of MHCI molecule and thus expand the memory specific B and T cells. The model MITD‐based mRNA vaccines encoding binding receptor‐binding domain (RBD) of SARS‐CoV‐2 were indeed found to achieve protective duration, optimal storage stability, broad efficacy, and high safety.

中文翻译：

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基于 MHCI 转运信号的 mRNA 疫苗加强对 RNA 病毒的免疫保护


主要组织相容性复合物 I 类 (MHCI) 运输信号 (MITD) 在增强 mRNA 疫苗功效方面发挥着关键作用。然而，缺乏研究探讨其增强对 RNA 病毒感染的免疫反应的功效。在这里，我们开发了一种用于 mRNA 疫苗配制的创新策略。这种方法涉及将 MITD 整合到编码病毒抗原的 mRNA 序列中。从机制上讲，基于 MITD 的 mRNA 疫苗可以通过模仿 MHCI 分子的动态运输特性来增强免疫保护，从而扩大记忆特异性 B 和 T 细胞。确实发现编码 SARS-CoV-2 结合受体结合域（RBD）的基于 MITD 的 mRNA 疫苗模型具有保护持续时间、最佳储存稳定性、广泛功效和高安全性。