Montgomery P C, Rafferty D E
Department of Immunology and Microbiology, Wayne State University School of Medicine, Detroit, Michigan 48201, USA.
Oral Microbiol Immunol. 1998 Jun;13(3):139-49. doi: 10.1111/j.1399-302x.1998.tb00725.x.
Bioadhesive degradable starch microparticles were used to deliver antigen and immunoglobulin A (IgA)-enhancing cytokines to the oral mucosa. Degradable starch microparticle immunization groups consisted of rats dosed topically at the sublingual epithelium of the oral cavity, by subcutaneous injection in the vicinity of the major salivary glands or by oral intubation with degradable starch microparticles containing dinitrophenyl-bovine serum albumin +/- IL-5/IL-6 +/- penetration enhancer (alpha-lysophosphatidylcholine). Dinitrophenyl-bovine serum albumin was also adsorbed onto alum for salivary gland vicinity injection and administered to the oral cavity in soluble form. Animals were subjected to 3 immunization cycles, and sequential samples were assayed by radioimmunoassay for salivary IgA, tear IgA and serum IgG anti-dinitrophenyl antibodies after secondary and tertiary immunization. Salivary IgA responses were highest in degradable starch microparticle groups receiving penetration enhancer at 71 days post-secondary immunization and continued in one degradable starch microparticle((oral cavity) and two injected (salivary gland vicinity) groups for up to 88 days post-tertiary immunization. Long-term tear responses were also observed in degradable starch microparticle groups receiving penetration enhancer, but they dissipated before the salivary gland-alum responses following tertiary immunization. Serum IgG responses were most pronounced in salivary gland groups, but long-term low level responses were detectable in oral cavity groups receiving degradable starch microparticle formulations with penetration enhancer. Inclusion of IL-5 and IL-6 in oral cavity-delivered degradable starch microparticle formulations consistently enhanced tear IgA while only upregulating salivary IgA antibody responses at early time points post immunization. IL-5 and IL-6 did not enhance serum IgG antibodies in any group. These data indicate that bioadhesive degradable starch microparticles can be used as a vehicle to deliver antigen and cytokine signals to the oral cavity and, when delivered in combination with a penetration enhancer, can potentiate long-term salivary IgA responses.
生物黏附性可降解淀粉微粒被用于将抗原和免疫球蛋白A（IgA）增强细胞因子递送至口腔黏膜。可降解淀粉微粒免疫组由经口腔舌下上皮局部给药、在主要唾液腺附近皮下注射或经口插管给予含有二硝基苯基 - 牛血清白蛋白+/-白细胞介素 - 5/白细胞介素 - 6+/-渗透增强剂（α - 溶血磷脂酰胆碱）的可降解淀粉微粒的大鼠组成。二硝基苯基 - 牛血清白蛋白也吸附在明矾上用于唾液腺附近注射，并以可溶形式给予口腔。动物接受3个免疫周期，在二次和三次免疫后，通过放射免疫分析法对唾液IgA、泪液IgA和血清抗二硝基苯基抗体进行连续样本检测。在二次免疫后71天，接受渗透增强剂的可降解淀粉微粒组的唾液IgA反应最高，并且在三次免疫后长达88天，一个可降解淀粉微粒（口腔）组和两个注射（唾液腺附近）组仍持续存在。在接受渗透增强剂的可降解淀粉微粒组中也观察到长期的泪液反应，但在三次免疫后，它们在唾液腺 - 明矾反应之前就消失了。唾液腺组的血清IgG反应最为明显，但在接受含有渗透增强剂的可降解淀粉微粒制剂的口腔组中可检测到长期的低水平反应。在经口腔递送的可降解淀粉微粒制剂中加入白细胞介素 - 5和白细胞介素 - 6持续增强泪液IgA，而仅在免疫后的早期时间点上调唾液IgA抗体反应。白细胞介素 - 5和白细胞介素 - 6在任何组中均未增强血清IgG抗体。这些数据表明，生物黏附性可降解淀粉微粒可作为一种载体，将抗原和细胞因子信号递送至口腔，并且当与渗透增强剂联合递送时，可增强长期的唾液IgA反应。
