Queensland Alliance for Agriculture and Food Innovation, The University of Queensland, St Lucia, QLD 4072, Australia.
Small. 2013 Sep 23;9(18):3138-46. doi: 10.1002/smll.201300012. Epub 2013 Apr 26.
Immunization to the model protein antigen ovalbumin (OVA) is investigated using MCM-41 mesoporous silica nanoparticles as a novel vaccine delivery vehicle and adjuvant system in mice. The effects of amino surface functionalization and adsorption time on OVA adsorption to nanoparticles are assessed. Amino-functionalized MCM-41 (AM-41) shows an effect on the amount of OVA binding, with 2.5-fold increase in binding capacity (72 mg OVA/g AM-41) compared to nonfunctionalized MCM-41 (29 mg OVA/g MCM-41). Immunization studies in mice with a 10 μg dose of OVA adsorbed to AM-41 elicits both antibody and cell-mediated immune responses following three subcutaneous injections. Immunizations at a lower 2 μg dose of OVA adsorbed to AM-41 particles results in an antibody response but not cell-mediated immunity. The level of antibody responses following immunization with nanoformulations containing either 2 μg or 10 μg of OVA are only slightly lower than that in mice which receive 50 μg OVA adjuvanted with QuilA, a crude mixture of saponins extracted from the bark of the Quillaja saponaria Molina tree. This is a significant result, since it demonstrates that AM-41 nanoparticles are self-adjuvanting and elicit immune responses at reduced antigen doses in vivo compared to a conventional delivery system. Importantly, there are no local or systemic negative effects in animals injected with AM-41. Histopathological studies of a range of tissue organs show no changes in histopathology of the animals receiving nanoparticles over a six week period. These results establish the biocompatible MCM-41 silica nanoparticles as a new method for vaccine delivery which incorporates a self-adjuvant effect.
以介孔二氧化硅纳米颗粒 MCM-41 作为新型疫苗给药载体和佐剂系统,研究了对模型蛋白抗原卵清蛋白(OVA)的免疫。评估了氨基表面功能化和吸附时间对纳米颗粒吸附 OVA 的影响。与非功能化 MCM-41(MCM-41)相比,氨基功能化 MCM-41(AM-41)对 OVA 结合量有影响,结合能力增加了 2.5 倍(AM-41 上 72mgOVA/g)。用吸附到 AM-41 上的 10μg OVA 进行的小鼠免疫研究,在进行三次皮下注射后,引起抗体和细胞介导的免疫反应。用吸附到 AM-41 颗粒上的 2μg OVA 进行低剂量(2μg)免疫接种会导致抗体反应,但不会引起细胞介导的免疫。用含有 2μg 或 10μg OVA 的纳米制剂免疫后,抗体反应水平仅略低于用 QuilA(Quillaja saponaria Molina 树皮中提取的粗皂素混合物)佐剂的 50μgOVA 免疫的小鼠。这是一个重要的结果,因为它表明 AM-41 纳米颗粒具有自身佐剂作用,并在体内与传统的给药系统相比,在减少抗原剂量的情况下引发免疫反应。重要的是,注射 AM-41 的动物没有局部或全身的负面效应。对一系列组织器官的组织病理学研究表明,在六周的时间内,接受纳米颗粒的动物的组织病理学没有变化。这些结果确立了生物相容的 MCM-41 二氧化硅纳米颗粒作为一种新的疫苗给药方法,该方法具有自身佐剂作用。