Excellent adjuvants and proper immunization routes play pivotal roles in activating a robust immune response. Nano-adjuvants have the advantages of enhancing immunogenicity, targeting delivery, and improving stability to provide a new solution for vaccine delivery. In this work, we designed and synthesized a pro-immunostimulant of liposolubility imiquimod derivative IMQP, which was synthesized by reaction of palmitoyl chloride with parent imiquimod (IMQ). Using an inactivated foot-and-mouth disease virus (FMDV) as antigen, and the as-synthesized IMQP containing long carbon chain as nano-adjuvant, we formulated a self-assembled foot-and-mouth disease nano-vaccine (IMQP@FMDV) by re-precipitation method for intradermal (I.D.) immunity vaccination. Because of its small size (∼131.75 ± 41.70 nm) and fat-soluble, the as-fabricated lipid nanoparticles (LNPs) showed promising potential for efficient delivery of antigens to immune cells. Also, lysosomal escape was confirmed by co-localization dendritic cells (DCs). Our findings demonstrated that IMQP nano-adjuvant greatly promoted the expression and secretion of cytokines and chemokines with a balance Th1/Th2 immune response via the I.D. administration. Meanwhile, due to the slowly releasing of IMQ by the hydrolysis of IMQP, IMQP persistently stimulated antigen-presenting cells (APCs) maturation and promoted antigen presentation, and subsequently induced the activation of the related downstream NF-кB and MAPK pathways of the TLR7 signaling pathway, thereby stimulated a robust both humoral and cellular immune response.

Read more: https://doi.org/10.1016/j.mtbio.2025.101567