An inoculation site-retained mRNA vaccine induces robust immune responses against SARS-CoV-2 variants
JOURNAL OF CONTROLLED RELEASE(2024)
摘要
mRNA-based vaccines and therapeutic agents hold great promise in prevention and treatment of human diseases, yet high percentage of systemic adverse effect in clinic remains a big safety concern. One major potential cause is a high level of leakage of the locally inoculated mRNA vaccine nanoparticles into circulation. We have screened and optimized a core-shell structured lipopolyplex (LPP) formulation for mRNA with a tissue-retention property. Upon intramuscular inoculation, the mRNA-encapsulated LPP nanoparticles were preferentially taken up by the phagocytic antigen-presentation cells, and potently promoted dendritic cell maturation. We applied the new formulation to prepare a prophylactic vaccine for SARS-CoV-2, and observed potent humoral and cellular immune responses from the vaccine in both murine models and non-human primates. More importantly, the vaccine demonstrated a benign safety profile in non-human primates, with limited side effects after repeated treatment with high dosages of LPP/mRNA. Taken together, the inoculation site-retained vaccine formulation serves as a promising vehicle for mRNA vaccines and therapeutic agents.
更多查看译文
关键词
mRNA vaccine,Inoculation site -retained nanoparticle,COVID-19,SARS-CoV-2
AI 理解论文
溯源树
样例
生成溯源树,研究论文发展脉络
Chat Paper
正在生成论文摘要