A lipid nanoparticle platform incorporating trehalose glycolipid for exceptional mRNA vaccine safety  

作　　者：Seo-Hyeon Bae Soyeon Yoo Jisun Lee Hyo-Jung Park Sung Pil Kwon Harin Jin Sang-In Park Yu-Sun Lee Yoo-Jin Bang Gahyun Roh Seonghyun Lee Sue Bean Youn In Woo Kim Ho Rim Oh Ashraf K.El-Damasy Gyochang Keum Hojun Kim Hyewon Youn Jae-Hwan Nam Eun-Kyoung Bang 

机构地区：[1]Department of Medical and Biological Sciences,The Catholic University of Korea,Gyeonggi-do,Bucheon,Republic of Korea [2]BK Four Department of Biotechnology,The Catholic University of Korea,Gyeonggi-do,Bucheon,Republic of Korea [3]Center for Brain Technology,Brain Science Institute,Korea Institute of Science and Technology(KIST),Seoul,02792,Republic of Korea [4]Center for Advanced Biomolecular Recognition,Korea Institute of Science and Technology(KIST),Seoul,02792,Republic of Korea [5]Division of Bio-Medical Science and Technology,KIST School,University of Science and Technology(UST),Seoul,Republic of Korea [6]SML Biopharm,Gwangmyeong,14353,Republic of Korea [7]KHU-KIST Department of Converging Science and Technology,Graduate School,Kyung Hee University,Seoul,02447,Republic of Korea [8]Cancer Research Institute,Seoul National University College of Medicine,Seoul,03080,Republic of Korea [9]Department of Nuclear Medicine,Cancer Imaging Center,Seoul National University Hospital,Seoul,03080,Republic of Korea

出　　处：《Bioactive Materials》2024年第8期486-498,共13页生物活性材料（英文）

基　　金：supported by a National Research Foundation of Korea(NRF)grant funded by the Korean government(MSIT)(No.NRF-2021M3E5E3080563,RS-2023-00229101);the Ministry of Food and Drug Safety(No.22213MFDS421);the Korea Institute of Science and Technology(KIST)Institutional Program(No.2E32852);H.Kim was supported by a National Research Foundation of Korea(NRF)grant funded by the Korean government(MSIT)(No.RS-2023-00209955);the Korea Institute of Science and Technology(KIST)Institutional Program(No.2E33111);J.H.Nam was supported by grants from the Ministry of Food and Drug Safety(grant number 22213MFDS421);partially supported by the Brain Korea 21 Four Program.H.Youn was supported by a grant from the Ministry of Food and Drug Safety(RS-2023-00217026).

摘　　要：The rapid development of messenger RNA(mRNA)vaccines formulated with lipid nanoparticles(LNPs)has contributed to control of the COVID-19 pandemic.However,mRNA vaccines have raised concerns about their potential toxicity and clinical safety,including side effects,such as myocarditis,anaphylaxis,and pericarditis.In this study,we investigated the potential of trehalose glycolipids-containing LNP(LNP S050L)to reduce the risks associated with ionizable lipids.Trehalose glycolipids can form hydrogen bonds with polar biomolecules,allowing the formation of a stable LNP structure by replacing half of the ionizable lipids.The efficacy and safety of LNP S050L were evaluated by encapsulating the mRNA encoding the luciferase reporter gene and measuring gene expression and organ toxicity,respectively.Furthermore,mice immunized with an LNP S050L-formulated mRNA vaccine expressing influenza hemagglutinin exhibited a significant reduction in organ toxicity,including in the heart,spleen,and liver,while sustaining gene expression and immune efficiency,compared to conventional LNPs(Con-LNPs).Our findings suggest that LNP S050L,a trehalose glycolipid-based LNP,could facilitate the development of safe mRNA vaccines with improved clinical safety.

关 键 词：Trehalose glycolipid Lipid nanoparticle mRNA vaccine Toxicity IMMUNOGENICITY 

分 类 号：R186[医药卫生—流行病学]