Liposome-mediated simvastatin in vaccine adjuvants: Its application and mechanism

  • Mol Immunol. 2026 Feb:190:72-85. doi: 10.1016/j.molimm.2026.01.002.
Zhijie Chen  1 ,  Zhiwu Xia  2 ,  Liping Chen  3 ,  Qingqing Nie  1 ,  Wang Gong  1 ,  Wenqiang Cao  1 ,  Xue Wang  1 ,  Yuehong Zou  1 ,  Shuai Zhang  1 ,  Yuchen Yang  1 ,  Menghong Yang  1 ,  Jiaming Yang  1 ,  Yanna Liu  1 ,  Lehong Zhang  1 ,  Wenjie Fang  1 ,  Yixin Chen  1 ,  Junlong Zhao  4 ,  Ziyan Meng  5
Affiliations
  • 1. Key Laboratory of Green and Healthy Livestock and Poultry Breeding Technology of Jiangxi Education Institutes, School of Animal Science, Ganzhou polytechnic college, Ganzhou, Jiangxi Province 341000, China.
  • 2. National Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei Province 430070, China.
  • 3. Department of Reproductive Medicine, Ganzhou People's Hospital, Ganzhou, Jiangxi province 341199, China.
  • 4. National Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei Province 430070, China. Electronic address: [email protected].
  • 5. Key Laboratory of Green and Healthy Livestock and Poultry Breeding Technology of Jiangxi Education Institutes, School of Animal Science, Ganzhou polytechnic college, Ganzhou, Jiangxi Province 341000, China. Electronic address: [email protected].
PMID: 41539277 DOI: 10.1016/j.molimm.2026.01.002
Abstract

To mitigate the APC cytotoxicity associated with simvastatin (a promising Adjuvant candidate), we encapsulated this drug in liposomes to generate LIPO-SIM, and explored the potential and mechanism. Formulated via ethanol injection and rotary evaporation, liposome-SIM was characterized for appearance, ζ-average, PDI, zeta potential, and encapsulation efficiency. C57BL/6 J mice were immunized with LIPO-SIM + OVA (0/21-day schedule), euthanized on day 28 to evaluate immunogenicity, safety, and antigen presentation mechanisms. In vitro, DC2.4 cells stimulated with liposome-SIM underwent RNA-Seq, metabolomics, and western blotting to clarify Adjuvant mechanisms. Results showed liposome-SIM significantly increased anti-OVA IgG titers and cellular immunity, activated local lymph node macrophages/dendritic cells, and enhanced MHC-I presentation. In vitro, AMPK inhibition and NF-κB activation were observed. No organ toxicity or inflammatory storms were detected. Liposome-SIM enhances cellular immunity via the MHC-I pathway, with AMPK/NF-κB signaling as a potential key mechanism.

Keywords
Adjuvant; Liposome; NF-Kappa B signaling pathway; Simvastatin; Vaccine.
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