Dayalbagh Educational Institute, Dayalbagh, Agra 282 005, India.
The Advanced Treatments Institute, Tassilostr. 3, 82131 Gauting, Germany.
Eur J Pharm Sci. 2014 Jun 2;56:55-64. doi: 10.1016/j.ejps.2014.01.006. Epub 2014 Feb 18.
A non-invasive, intra/transcutaneous immunisation of mice with a suitable combination of tetanus toxoid, ultradeformable vesicle (Transfersome®) carrier, and monophosphoryl lipid A adjuvant targets immuno-competent cells in a body and can protect 100% of the tested mice against an otherwise lethal (50×LD50) parenteral tetanus toxin challenge. The late immune response to the epicutaneously applied tetanus toxoid in such vesicles consists chiefly of circulating IgG1 and IgG2b antibody isotypes, indicative of a specific Th2 cellular response bias. Immunisations by subcutaneous injections moreover protect 100% of mice against a similar, otherwise lethal, dose of tetanus toxin. However, the immune response to transcutaneous and invasive immunisation differs. The latter elicits mainly IgG1 and IgG2b as well as IgG2a antibody isotypes, indicative of a mixed Th1/Th2 response. The cytokine response of the intra/transcutaneously and subcutaneously immunised mice reflects the difference in the organ-specific manner. IFN-γ concentration is appreciably increased in the draining lymph nodes and IL-10 in spleen. Since tetanus is a neutral antigen, both the Th1-specific IFN-γ and the Th-2 specific-IL-10 are observable.
采用破伤风类毒素、超变形囊泡(Transfersome®)载体和单磷酰脂质 A 佐剂的合适组合对小鼠进行非侵入性、经皮/透皮免疫,可靶向体内免疫活性细胞,并可保护 100%的受试小鼠免受致命(50×LD50)的破伤风毒素的攻击。在这种囊泡中,经皮应用破伤风类毒素后的晚期免疫反应主要由循环 IgG1 和 IgG2b 抗体同种型组成,表明存在特定的 Th2 细胞反应偏向。此外,通过皮下注射进行免疫可使 100%的小鼠免受类似的、致命的破伤风毒素剂量的影响。然而,经皮和经皮免疫的免疫反应不同。后者主要引发 IgG1 和 IgG2b 以及 IgG2a 抗体同种型,表明存在混合的 Th1/Th2 反应。经皮/透皮和皮下免疫的小鼠的细胞因子反应反映了器官特异性方式的差异。IFN-γ 浓度在引流淋巴结中显著增加,IL-10 在脾脏中增加。由于破伤风是一种中性抗原,因此可以观察到 Th1 特异性 IFN-γ 和 Th2 特异性-IL-10。