Bioactive Materials (Aug 2024)

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

  • 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

Journal volume & issue
Vol. 38
pp. 486 – 498

Abstract

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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.

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