University of Washington, Seattle, WA, 98195-5061, USA.
Macromol Biosci. 2019 Feb;19(2):e1800242. doi: 10.1002/mabi.201800242. Epub 2018 Nov 16.
mRNA vaccines have proven to be more stable, effective, and specific than protein/peptide-based vaccines in stimulating both humoral and cellular immune response. However, mRNA's fast degradation rate and low-transfection efficiency in vivo impede its potential in vaccination. Recent research in gene delivery has focused on nonviral vaccine carriers and either implantable or injectable delivery systems to improve transgene expression in vivo. Here, an injectable chitosan-alginate gel scaffold for the local delivery of mRNA vaccines is reported. Gel scaffold biodegradation rates and biocompatibility are quantified. Scaffold-mediated mRNA in vivo transgene expression as well as ovalbumin antigen specific cellular and humoral immune responses are evaluated in vivo. Luciferase reporter protein expression resulting from mRNA lipoplex-loaded gel scaffolds is five times higher than systemic injection. Compared to systemic injections of naked mRNA or mRNA:lipoplexes, elevated levels of T cell proliferation and IFN-γ secretion are seen with in vivo scaffold-mediated mRNA lipoplex delivery. Furthermore, a humoral response (ovalbumin antigen specific IgG levels) is observed as early as week 1 for scaffold-mediated mRNA lipoplex delivery, while protein-based immunization did not elicit IgG production until 2 weeks post-injection. Results suggest that injectable scaffold mRNA vaccine delivery maybe a viable alternative to traditional nucleic acid immunization methods.
mRNA 疫苗在刺激体液和细胞免疫反应方面比基于蛋白质/肽的疫苗更稳定、有效和特异。然而,mRNA 在体内的快速降解率和低转染效率阻碍了其在疫苗接种方面的潜力。最近的基因传递研究集中在非病毒疫苗载体和可植入或可注射的递送系统上,以提高体内转基因的表达。本文报道了一种用于 mRNA 疫苗局部递送的可注射壳聚糖-海藻酸钠凝胶支架。定量了凝胶支架的生物降解率和生物相容性。在体内评估了支架介导的 mRNA 体内转基因表达以及卵清蛋白抗原特异性细胞和体液免疫反应。负载 mRNA 脂质体的凝胶支架的报告蛋白表达比全身注射高五倍。与全身注射裸 mRNA 或 mRNA:脂质体相比,体内支架介导的 mRNA 脂质体递送可观察到 T 细胞增殖和 IFN-γ 分泌水平升高。此外,支架介导的 mRNA 脂质体递送可在第 1 周观察到体液反应(卵清蛋白抗原特异性 IgG 水平),而蛋白免疫直到注射后 2 周才引起 IgG 产生。结果表明,可注射支架 mRNA 疫苗递送可能是传统核酸免疫方法的可行替代方案。
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