mRNA 疫苗的功效和安全性都依赖于特定体液和细胞免疫反应的微调。我们没有调整疫苗成分，而是提出了佐剂效应的时间顺序管理的概念，以调节受自然病毒感染启发的适应性免疫效力和偏好。通过模拟病毒感染过程中 I 型干扰素表达动态，开发了三种采用不同佐剂和 mRNA 暴露序列的疫苗策略，即 Precede、Coincide 和 Follow。接下来，在 mRNA 之后施用佐剂的策略有效地抑制了肿瘤进展，这归因于增强的 mRNA 翻译、增强的 p-MHC I 表达和升高的 CD8 T 细胞反应。与此同时，Follow 表现出更高的生物安全性，其特点是心脏和肝脏毒性的发生率降低，因为它改变了连续注射之间的疫苗接种微环境。我们的策略强调了微调佐剂效应动态在优化 mRNA 疫苗临床应用中的重要性。

The efficacy and safety of mRNA vaccines both rely on a fine-tuning of specific humoral and cellular immune responses. Instead of adjustments in vaccine component, we proposed a concept of chronological management of adjuvant effect to modulate the adaptive immune potency and preference inspired by natural virus infection. By simulating type I interferon expression dynamics during viral infection, three vaccine strategies employing distinct exposure sequences of adjuvant and mRNA have been developed, namely Precede, Coincide, and Follow. Follow, the strategy of adjuvant administration following mRNA, effectively suppressed tumor progression, which was attributed to enhanced mRNA translation, augmented p-MHC I expression, and elevated CD8+ T cell response. Meanwhile, Follow exhibited improved biosafety, characterized by reduced incidences of cardiac and liver toxicity, owing to its alteration to the vaccination microenvironment between successive injections. Our strategy highlights the importance of fine-tuning adjuvant effect dynamics in optimizing mRNA vaccines for clinical application.