Abstract: mRNA vaccine is a recombinant vaccine that mimics the structure and function of natural mRNA, introduces the gene of interest into the body, and prevents and or treats diseases by inducing an immune response. Using lipid nanoparticle(LNP) as delivery vehicles, the efficacy, safety and production efficiency of mRNA vaccines have been dramatically improved, while maintaining the stability of mRNA vaccines and improving the targeting of the vaccines. mRNA-LNP delivery technology has continuously demonstrated its innovative results in recent years in the therapeutic areas of different diseases, but also faces multiple technical difficulties and biological challenges due to its unique immune activation mechanism. The mRNA-LNP delivery technology is facing multiple technical and biological challenges. Different therapeutic targets have different requirements on the delivery system and mode of mRNA vaccines, and the correlation between the delivery system and the immune activation mechanism of the vaccine has become the key to optimize the design of vaccines. This article summarizes the immune activation mechanisms of vaccines delivered by mRNA-LNP delivery systems, and propose to provide new ideas and potential solutions for the future screening of lipid combinations targeting specific immune nodes by artificial intelligence or customized design of the next-generation delivery systems with both high efficiency and safety.