Wang Yutao, Li Lei, Liang Min, Liu Gan, Lu Yinying
302 Clinical Medical School, Peking University, Beijing 100039, China.
Senior Department of Hepatology, The Fifth Medical Center of PLA General Hospital, Beijing 100039, China.
Vaccines (Basel). 2025 May 18;13(5):537. doi: 10.3390/vaccines13050537.
: The COVID-19 pandemic has brought mRNA vaccines to the forefront due to their widespread use. In this study, we explored the potential advantages of the self-amplifying mRNA (saRNA) vaccine over conventional mRNA vaccines. : Initially, we optimized lipid nanoparticle formulations and employed dT20 affinity chromatography purification to improve the intracellular expression of saRNA. Subsequently, we demonstrated that saRNA exhibited sustained expression for up to one month, both in vitro and in vivo, in contrast to mRNA. Finally, we developed a saRNA-based COVID-19 vaccine and achieved superior immune protection in mice compared to mRNA vaccine by co-delivering the B18R-encoding mRNA. : The co-delivery of B18R-mRNA with the saRNA vaccine significantly enhanced neutralizing antibody responses, outperforming those induced by the mRNA vaccine alone. This co-delivery strategy effectively regulated the early innate immune activation triggered by saRNA, facilitating a more robust adaptive immune response. : The optimization strategies we used in this study highlight the potential of saRNA vaccines to offer stronger and more durable immune protection. The insights gained from this study not only promote the advancement of saRNA vaccine development but also provide practical guidance for their broader application in the fight against infectious diseases.
由于其广泛使用，新冠疫情使信使核糖核酸（mRNA）疫苗成为焦点。在本研究中，我们探究了自我扩增信使核糖核酸（saRNA）疫苗相对于传统信使核糖核酸疫苗的潜在优势。最初，我们优化了脂质纳米颗粒配方，并采用dT20亲和层析纯化法来提高saRNA在细胞内的表达。随后，我们证明，与信使核糖核酸不同，saRNA在体外和体内均表现出长达一个月的持续表达。最后，我们研发了一种基于saRNA的新冠疫苗，通过共同递送编码B18R的信使核糖核酸，在小鼠体内实现了比信使核糖核酸疫苗更好的免疫保护。B18R信使核糖核酸与saRNA疫苗共同递送显著增强了中和抗体反应，优于单独使用信使核糖核酸疫苗所诱导的反应。这种共同递送策略有效地调节了由saRNA触发的早期先天免疫激活，促进了更强有力的适应性免疫反应。我们在本研究中使用的优化策略凸显了saRNA疫苗提供更强有力和更持久免疫保护的潜力。从本研究中获得的见解不仅推动了saRNA疫苗研发的进展，也为其在抗击传染病中的更广泛应用提供了实际指导。
