State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, PR China; University of Chinese Academy of Sciences, Beijing 100049, PR China.
State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, PR China.
Vaccine. 2020 Mar 4;38(11):2478-2486. doi: 10.1016/j.vaccine.2020.02.004. Epub 2020 Feb 10.
In this work, we explored the potential of cationic solid lipid nanoparticles (cSLN) as efficient adjuvants for inactivated foot and mouth disease virus (iFMDV) vaccine. The cSLN were prepared by O/W emulsion method with Compritol 888 ATO as lipid matrix, and were modified by cationic lipid Didodecyldimethylammonium bromide (DDAB). The content of cationic lipid was optimized to produce cSLN with appropriate particle size, surface morphology, zeta potential, and polydispersity. Loading iFMDV onto cSLN by electrostatic attraction did not destruct iFMDV particle structure as measured by high performance size exclusion chromatography (HPSEC). Differential scanning fluorimetry (DSF) showed the transition temperature, T, related to iFMDV dissociation increased for 1.2 °C after loading on cSLN, indicating an enhanced stability of this unstable antigen. The cSLN loaded iFMDV enhanced in vitro antigen uptake and activation of bone-marrow-derived dendritic cells (BMDCs) with augmented expression of CD86, CD40, and MHC I. In animal trials, BALB/c mice were immunized with free iFMDV, antigen adjuvanted with the cSLN, and antigen adjuvanted with Montanide ISA 206 emulsion. Specific antibody titers showed cSLN could stimulate similar FMDV-specific IgG and IgG subclasses antibody level compared with the widely used ISA 206. In addition, cSLN significantly enhanced memory immune response including effector-memory T cells and central-memory T cells compared to free iFMDV antigen and antigen adjuvanted with ISA 206. Taken together the enhanced humoral and T cell immune responses and the antigen structure friendly properties, cSLN can be a potential adjuvant for iFMDV vaccines.
在这项工作中，我们探索了阳离子固体脂质纳米粒（cSLN）作为口蹄疫病毒（iFMDV）灭活疫苗有效佐剂的潜力。cSLN 是通过 O/W 乳液法制备的，以 Compritol 888 ATO 为脂质基质，并通过阳离子脂质双十二烷基二甲基溴化铵（DDAB）进行修饰。优化阳离子脂质的含量，以产生具有适当粒径、表面形态、Zeta 电位和多分散性的 cSLN。通过静电吸引将 iFMDV 加载到 cSLN 上，不会破坏 HPSEC 测量的 iFMDV 颗粒结构。差示扫描荧光法（DSF）显示，iFMDV 加载到 cSLN 后，与 iFMDV 解离相关的转变温度 T 升高了 1.2°C，表明这种不稳定抗原的稳定性增强。负载 iFMDV 的 cSLN 增强了体外抗原摄取和骨髓源性树突状细胞（BMDCs）的激活，同时增强了 CD86、CD40 和 MHC I 的表达。在动物试验中，BALB/c 小鼠用游离 iFMDV、用 cSLN 佐剂的抗原和用 Montanide ISA 206 乳剂佐剂的抗原进行免疫。特异性抗体滴度显示，cSLN 可刺激与广泛使用的 ISA 206 相似的 FMDV 特异性 IgG 和 IgG 亚类抗体水平。此外，与游离 iFMDV 抗原和用 ISA 206 佐剂的抗原相比，cSLN 显著增强了记忆免疫应答，包括效应记忆 T 细胞和中央记忆 T 细胞。综上所述，增强的体液和 T 细胞免疫应答以及抗原结构友好性，cSLN 可为 iFMDV 疫苗提供一种有潜力的佐剂。
