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DOTAP and DP7-C liposomes

Vaxjo ID 229       
Vaccine Adjuvant Name DOTAP and DP7-C liposomes       
Adjuvant VO ID VO_0005716
Description DP7-C-modified DOTAP liposomes function as a dual-use system—mRNA delivery vehicle and immune adjuvant, improving antigen presentation and immune responses       
Stage of Development Research       
Host Species for Testing Mouse       
Components As a carrier of mRNA, DP7-C-modified DOTAP liposomes (DOTAP/DP7-C) could transfer mRNA efficiently into different type of DCs in vitro.       
Structure Cationic liposomes (~100 nm) composed of DOTAP, cholesterol, and surface-bound DP7-C peptide       
Appearance Well-dispersed nanoparticles; visualized by TEM as spherical vesicles       
Storage Stable at 4°C for up to 6 months       
Preparation DOTAP and cholesterol co-dissolved in chloroform → dried into lipid film → rehydrated with DP7-C in water (thin-film dispersion method)       
Dosage mRNA: 10 µg Liposomes: 20 µg per dose (subcutaneous injection in mice)       
Function As an immunoadjuvant, DOTAP/DP7-C liposomes were shown to be more efficacious in stimulating DC maturation, CD103+ DC (contributing to antigen presentation) production and proinflammatory cytokine secretion than DOTAP liposomes both in vitro and in vivo. In animal studies, the subcutaneous administration of DOTAP/DP7-C/LL2 neoantigen-encoding mRNA complexes significantly inhibited the growth of LL2 in situ and the growth of subcutaneous tumors and stimulated the production of antigen-specific lymphocyte reactions, which were superior to the DOTAP/LL2 neoantigen-encoding mRNA complex group. In conclusion, DOTAP/DP7-C liposomes may serve as a potential universal mRNA delivery system, providing a simple method to increase the efficiency of intracellular mRNA delivery and the immunostimulatory activity of DCs       
Safety Low toxicity in vitro and in vivo; higher IC50 (>100 µg/mL) compared to Lipo2000 and PEI25K       
References
Zhang et al., 2020: Zhang R, Tang L, Tian Y, Ji X, Hu Q, Zhou B, Ding Z, Xu H, Yang L. DP7-C-modified liposomes enhance immune responses and the antitumor effect of a neoantigen-based mRNA vaccine. Journal of controlled release : official journal of the Controlled Release Society. 2020; 328; 210-221. [PubMed: 32860927].