Bionanoparticle‐Based Delivery in Antihypertensive Vaccine Mediates DC Activation through Lipid‐Raft Reorganization

Abstract

Bionanoparticles (BNPs) are widely used as vaccine carriers. Compared with classic protein carriers, BNPs exhibit nanostructures that enable them to interaction with biointerface-like cell membrane or membrane domains. An antihypertensive vaccine ATR-NP is produced based on a virus-like particle (VLP) Qβ carrier. Qβ shows great delivery efficiency and immunogenicity to antigen-presenting cells (APCs) such as dendritic cells (DCs), and DC activation induced by ATR-NP is highly dependent on membrane lipid rafts. Further studies reveal that ATR-NP exhibits tight affinity to rafts, and interface effects between them prompt membrane phase separation and raft accumulation through NP-induced membrane curvature change. Lipid rafts are accumulated and expanded together with a decline of their diffusion in membrane,which benefits signaling protein Src partition in rafts. The heterogeneous protein partition implies functional centralization for stronger signal transduction. In conclusion, targeting and reorganizing membrane domains such as lipid rafts suggests BNPs could be used as vaccine carriers and is a potent strategy for vaccine and other immunological agent design.

Recent progress in targeted delivery vectors based on biomimetic nanoparticles

“…dP@Qβ VNP/RNAi bypassed BBB to deliver RNAi that had an inhibiting effect on DNA reparation, which exhibited synergy with temozolomide in intracranial glioblastomas mice models. In another recent piece of work, an antihypertensive vaccine was designed based on the conjugation of Qβ VNPs and a peptide from Angiotensin II receptor 1 (ATR-Qβ VNPs) 236 . Through a specific dendritic cell functional regulation route over lipid raft reorganization, ATR-Qβ VNPs vaccine stimulated high-titer antibodies aiming at AT1R and decreased systolic blood pressure in hypertensive mice models.…”

The dream for therapeutic vaccines for cardiovascular diseases

“…本团队研发的疫 苗提呈抗原短肽均是由7~12个氨基酸组成的单个表 位, 免疫过程不使用佐剂, 免疫间隔时间至少2周, 疫苗 免疫后Tfh明显活化但不过度, CD8 + T细胞未见增加, 多器官组织切片及肾脏电子显微镜切片均未见炎症及 免疫复合物沉积相关损伤 [16,21,22,34] , 多方面展示了多肽 偶联疫苗的免疫安全性. 其他疫苗研发团队, 如Naka-gami等人 [9,78] [68] , 活化后DC可有效激活T辅助细胞. 同时疫苗被巨噬细胞及B细胞捕获并提呈给滤泡区FDC细胞 促进B细胞增殖活化, 联合T细胞的辅助作用共同诱导B细胞分化为具有分泌高亲和力抗原肽特异性抗体的浆细胞和具有长期 记忆功能的记忆性B细胞 Figure 2 Immune responses of peptide conjugated vaccines.…”

“…Peptide conjugated vaccines using VLP nanoparticles as the carrier can be quickly recognized by unspecific immunity. Nanoparticle vaccine activates DCs efficiently via lipid raft dependent pathway [68] . Mature DCs present peptide-MHC II complex to effectively activate T helper cells.…”

Artificial Engineering of Immune Cells for Improved Immunotherapy

“…Using biomaterials for in vivo vaccine delivery toward internal DCs is among the most used approach to improve therapeutic outcomes of DCs‐based immunotherapy. [ 56–59 ] Another important strategy is to in vivo introduce man‐made scaffolds to provide a benign microenvironment for DC recruitment, activation, and transplantation. [ 60,61 ] For example, self‐assembled peptide‐based hydrogels and mesoporous silica microrods (MSRs) can not only provide an artificial niche for DCs, but also form a reservoir for local delivery of therapeutic drugs for combination therapy.…”