Division of Enzyme Chemistry, Institute for Enzyme Research, Tokushima University, Tokushima, Japan.
Division of Enzyme Chemistry, Institute for Enzyme Research, Tokushima University, Tokushima, Japan.
Vaccine. 2019 Jan 21;37(4):612-622. doi: 10.1016/j.vaccine.2018.12.002. Epub 2018 Dec 13.
We reported previously that a synthetic mucosal adjuvant SF-10, which mimics human pulmonary surfactant, delivers antigen to mucosal dendritic cells in the nasal cavity and promotes induction of humoral and cellular immunity. The aim of the present study was to determine the effects of oral administration of antigen combined with SF-10 (antigen-SF-10) on systemic and local immunity. Oral administration of ovalbumin, a model antigen, combined with SF-10 enhanced ovalbumin uptake into intestinal antigen presenting MHC IICD11c cells and their CD11bCD103 and CD11bCD103 subtype dendritic cells, which are the major antigen presenting subsets of the intestinal tract, more efficiently compared to without SF-10. Oral vaccination with influenza hemagglutinin vaccine (HAv)-SF-10 induced HAv-specific IgA and IgG in the serum, and HAv-specific secretory IgA and IgG in bronchoalveolar lavage fluid, nasal washes, gastric extracts and fecal material; their levels were significantly higher than those induced by subcutaneous HAv or intranasal HAv and HAv-SF-10 vaccinations. Enzyme-linked immunospot assay showed high numbers of HAv-specific IgA and IgG antibody secreting cells in the gastrointestinal and respiratory mucosal lymphoid tissues after oral vaccination with HAv-SF-10, but no or very low induction following oral vaccination with HAv alone. Oral vaccination with HAv-SF-10 provided protective immunity against severe influenza A virus infection, which was significantly higher than that induced by HAv combined with cholera toxin. Oral vaccination with HAv-SF-10 was associated with unique cytokine production patterns in the spleen after HAv stimulation; including marked induction of HAv-responsive Th17 cytokines (e.g., IL-17A and IL-22), high induction of Th1 cytokines (e.g., IL-2 and IFN-γ) and moderate induction of Th2 cytokines (e.g., IL-4 and IL-5). These results indicate that oral vaccination with HAv-SF-10 induces more efficient systemic and local immunity than nasal or subcutaneous vaccination with characteristically high levels of secretory HAv-specific IgA in various mucosal organs and protective immunity.
我们之前曾报道过，一种合成的黏膜佐剂 SF-10，模拟人类肺表面活性剂，可将抗原递呈给鼻腔中的黏膜树突状细胞，并促进体液和细胞免疫的诱导。本研究的目的是确定抗原与 SF-10（抗原-SF-10）联合口服给药对系统和局部免疫的影响。口服卵清蛋白（一种模型抗原）与 SF-10 联合给药可更有效地增强肠道抗原呈递 MHC IIICD11c 细胞及其 CD11bCD103 和 CD11bCD103 亚型树突状细胞摄取卵清蛋白，而不使用 SF-10 则不然。口服流感血凝素疫苗（HAv）-SF-10 疫苗可诱导血清中产生 HAv 特异性 IgA 和 IgG，以及支气管肺泡灌洗液、鼻洗液、胃提取物和粪便中的 HAv 特异性分泌型 IgA 和 IgG；其水平明显高于皮下 HAv 或鼻内 HAv 和 HAv-SF-10 接种诱导的水平。酶联免疫斑点法显示，口服 HAv-SF-10 疫苗接种后，胃肠道和呼吸道黏膜淋巴组织中 HAv 特异性 IgA 和 IgG 抗体分泌细胞数量较高，但单独口服 HAv 疫苗接种则没有或很少诱导。口服 HAv-SF-10 疫苗接种可提供针对严重流感 A 病毒感染的保护免疫，其效果明显高于 HAv 与霍乱毒素联合接种。口服 HAv-SF-10 疫苗接种后与脾内 HAv 刺激后独特的细胞因子产生模式相关；包括 HAv 反应性 Th17 细胞因子（如 IL-17A 和 IL-22）的显著诱导、Th1 细胞因子（如 IL-2 和 IFN-γ）的高诱导和 Th2 细胞因子（如 IL-4 和 IL-5）的适度诱导。这些结果表明，与鼻内或皮下接种相比，口服 HAv-SF-10 疫苗接种可诱导更有效的系统和局部免疫，且在各种黏膜器官中具有特征性高水平的分泌型 HAv 特异性 IgA 和保护性免疫。
