Suzuki Kengo, Yoshizaki Yuta, Horii Kenta, Murase Nobuo, Kuzuya Akinori, Ohya Yuichi
Faculty of Chemistry, Materials, and Bioengineering, Kansai University, 3-3-35 Yamate, Suita, Osaka 564-8680, Japan.
Organization for Research and Development of Innovative Science and Technology (ORDIST), Kansai University, 3-3-35 Yamate, Suita, Osaka 564-8680, Japan.
Biomater Sci. 2022 Apr 12;10(8):1920-1928. doi: 10.1039/d1bm01985f.
Hyaluronic acid (HA)-coated biodegradable polymeric micelles were developed as nanoparticulate vaccine delivery systems to establish an effective nasal vaccine. We previously reported HA-coated micelles prepared by forming a polyion complex (PIC) of poly(L-lysine)--polylactide (PLys--PLA) micelles and HA. The HA-coated micelles exhibited specific accumulation in HA receptor-expressing cells and extremely high colloidal stability under diluted blood conditions. In this study, a model antigen, ovalbumin (OVA), and an adjuvant oligonucleotide containing the CG motif (CpG-DNA) were efficiently loaded in HA-coated micelles electrostatic interactions. HA-coated micelles delivered OVA and CpG-DNA in mouse bone marrow-derived dendritic cells (BMDCs) and resulted in the upregulation of mRNA encoding IFN-γ and IL-4 in BMDCs. In addition, HA-coated micelles enhanced the expression of the major histocompatibility complex (MHC) class II on BMDCs. We investigated the immune response of HA-coated micelles following intranasal administration. HA-coated micelles induced higher OVA-specific IgG in the blood and OVA-specific IgA in the nasal wash than control (carboxymethyl dextran-coated) micelles. These results suggest that HA-coated micelles efficiently deliver antigens and adjuvants to mucosal-resident immune cells. Therefore, HA-coated micelles are promising platforms for developing nasal vaccines against infectious diseases.
透明质酸（HA）包被的可生物降解聚合物胶束被开发为纳米颗粒疫苗递送系统，以建立有效的鼻用疫苗。我们之前报道了通过形成聚（L-赖氨酸）-聚乳酸（PLys-PLA）胶束与HA的聚离子复合物（PIC）制备的HA包被胶束。HA包被胶束在表达HA受体的细胞中表现出特异性积累，并且在稀释血液条件下具有极高的胶体稳定性。在本研究中，模型抗原卵清蛋白（OVA）和含CG基序的佐剂寡核苷酸（CpG-DNA）通过静电相互作用被有效地负载到HA包被胶束中。HA包被胶束将OVA和CpG-DNA递送至小鼠骨髓来源的树突状细胞（BMDCs），并导致BMDCs中编码IFN-γ和IL-4的mRNA上调。此外，HA包被胶束增强了BMDCs上主要组织相容性复合体（MHC）II类分子的表达。我们研究了鼻内给药后HA包被胶束的免疫反应。与对照（羧甲基葡聚糖包被）胶束相比，HA包被胶束在血液中诱导产生更高水平的OVA特异性IgG，在鼻腔灌洗液中诱导产生更高水平的OVA特异性IgA。这些结果表明，HA包被胶束可有效地将抗原和佐剂递送至黏膜驻留免疫细胞。因此，HA包被胶束是开发针对传染病的鼻用疫苗的有前景的平台。
