Joint Research Center for Food Nutrition and Health of IHM, School of Tea and Food Science & Technology, State Key Laboratory of Tea Plant Biology and Utilization, Anhui Agricultural University, Hefei 230036, PR China; Shenzhen Institute of Translational Medicine, Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University, Health Science Center, Shenzhen University, Shenzhen 518035, PR China.
Joint Research Center for Food Nutrition and Health of IHM, School of Tea and Food Science & Technology, State Key Laboratory of Tea Plant Biology and Utilization, Anhui Agricultural University, Hefei 230036, PR China.
J Control Release. 2024 Oct;374:39-49. doi: 10.1016/j.jconrel.2024.08.005. Epub 2024 Aug 8.
Immunological adjuvants are vaccine components that enhance long-lasting adaptive immune responses to weakly immunogenic antigens. Monophosphoryl lipid A (MPLA) is a potent and safe vaccine adjuvant that initiates an early innate immune response by binding to the Toll-like receptor 4 (TLR4). Importantly, the binding and recognition process is highly dependent on the monomeric state of MPLA. However, current vaccine delivery systems often prioritize improving the loading efficiency of MPLA, while neglecting the need to maintain its monomeric form for optimal immune activation. Here, we introduce a Pickering emulsion-guided MPLA monomeric delivery system (PMMS), which embed MPLA into the oil-water interface to achieve the monomeric loading of MPLA. During interactions with antigen-presenting cells, PMMS functions as a chaperone for MPLA, facilitating efficient recognition by TLR4 regardless of the presence of lipopolysaccharide-binding proteins. At the injection site, PMMS efficiently elicited local immune responses, subsequently promoting the migration of antigen-internalized dendritic cells to the lymph nodes. Within the draining lymph nodes, PMMS enhanced antigen presentation and maturation of dendritic cells. In C57BL/6 mice models, PMMS vaccination provoked potent antigen-specific CD8 T cell-based immune responses. Additionally, PMMS demonstrated strong anti-tumor effects against E.G7-OVA lymphoma. These data indicate that PMMS provides a straightforward and efficient strategy for delivering monomeric MPLA to achieve robust cellular immune responses and effective cancer immunotherapy.
免疫佐剂是增强对弱免疫原性抗原的长期适应性免疫反应的疫苗成分。单磷酰脂质 A (MPLA) 是一种有效的、安全的疫苗佐剂，通过与 Toll 样受体 4 (TLR4) 结合，引发早期固有免疫反应。重要的是，结合和识别过程高度依赖于 MPLA 的单体状态。然而，目前的疫苗传递系统通常优先提高 MPLA 的负载效率，而忽略了保持其单体形式以实现最佳免疫激活的需求。在这里，我们引入了一种 Pickering 乳液引导的 MPLA 单体传递系统 (PMMS)，将 MPLA 嵌入油水界面，实现 MPLA 的单体负载。在与抗原呈递细胞相互作用时，PMMS 作为 MPLA 的伴侣分子，无论是否存在脂多糖结合蛋白，都能有效地促进 TLR4 的识别。在注射部位，PMMS 可有效地引发局部免疫反应，随后促进内吞抗原的树突状细胞向淋巴结迁移。在引流淋巴结中，PMMS 增强了树突状细胞的抗原呈递和成熟。在 C57BL/6 小鼠模型中，PMMS 疫苗接种引发了强烈的抗原特异性 CD8 T 细胞免疫反应。此外，PMMS 对 E.G7-OVA 淋巴瘤表现出强烈的抗肿瘤作用。这些数据表明，PMMS 为递送单体 MPLA 提供了一种简单有效的策略，以实现强大的细胞免疫反应和有效的癌症免疫治疗。
