Artificial Nanolipid Droplets with Monolayer Lecithin Membranes and Vitamin E Cores as Vaccine Adjuvants

Lipid droplets (LDs) are organelles with good natural biocompatibility that are abundant in eukaryotic cells and are considered good candidates for use in biological delivery inside cells. Importantly, numerous studies have reported that LDs also participate in immune processes. Here, we investigated whether LDs can also be used as vaccine adjuvants. We designed and prepared a variety of artificial nano-LDs with a nanometer size (200–300 nm) to test this possibility. Artificial nano-LDs have the same monolayer lecithin membrane as natural LDs; in contrast to natural LDs, artificial nano-LDs do not have proteins on their surfaces, which is beneficial to ensure better biocompatibility. Compared with other oil-in-water emulsion adjuvants (MF59 [AddaVax] and AS03 [AddaS03] used in licensed vaccines), vitamin E was used instead of squalene as the oil phase. The artificial nano-LDs (V3, V11, and V12) prepared in this study have structures similar to those of MF59 (AddaVax) and AS03(AddaS03) under scanning electron microscopy and transmission electron microscopy and have better stability than MF59 (AddaVax) and AS03 (AddaS03); they can even withstand high-temperature sterilization at 120 °C for 30 min. In vivo test results showed that the artificial nano-LDs had good biocompatibility. Recombinant hepatitis B surface antigen and recombinant varicella-zoster virus glycoprotein E were used as model antigens to evaluate the adjuvant effect. We found that our artificial nano-LDs induced excellent humoral and cellular immunity (comparable to that of MF59 [AddaVax]). In addition, apart from the initial increase in the particle size upon high-temperature sterilization, the adjuvant effect of artificial nano-LDs did not decrease.