Center for Research in Molecular Medicine and Chronic Diseases (CIMUS), Department of Pharmacology, Pharmacy and Pharmaceutical Technology, School of Pharmacy , University of Santiago de Compostela , 15782 Santiago de Compostela , Spain.
Departamento de Farmacia, Facultad de Química , Pontificia Universidad Católica de Chile , Santiago , Chile.
Mol Pharm. 2018 Dec 3;15(12):5653-5664. doi: 10.1021/acs.molpharmaceut.8b00852. Epub 2018 Nov 19.
One of the main challenges in the development of vaccine has been to improve their stability at room temperature and eliminate the limitations associated with the cold chain storage. In this paper, we describe the development and optimization of thermostable nanocarriers consisting of an oily core with immunostimulating activity, containing squalene or α tocopherol surrounded by a protamine shell. The results showed that these nanocapsules can efficiently associate the recombinant hepatitis B surface antigen (rHBsAg) without compromising its antigenicity. Furthermore, the freeze-dried protamine nanocapsules were able to preserve the integrity and bioactivity of the associated antigen upon storage for at least 12 months at room temperature. In vitro studies evidenced the high internalization of the nanocapsules by immunocompetent cells, followed by cytokine secretion and complement activation. In vivo studies showed the capacity of rHBsAg-loaded nanocapsules to elicit protective levels upon intramuscular or intranasal administration to mice. Overall, our data indicate that protamine nanocapsules are an innovative thermostable nanovaccine platform for improved antigen delivery.
疫苗开发面临的主要挑战之一是提高其在室温下的稳定性，并消除与冷链储存相关的限制。本文描述了由具有免疫刺激活性的油性核心组成的热稳定纳米载体的开发和优化，该核心含有角鲨烯或α-生育酚，周围是鱼精蛋白壳。结果表明，这些纳米胶囊可以有效地将重组乙型肝炎表面抗原（rHBsAg）结合在一起，而不会损害其抗原性。此外，冷冻干燥的鱼精蛋白纳米胶囊在室温下储存至少 12 个月，仍能保持结合抗原的完整性和生物活性。体外研究证明了免疫活性细胞对纳米胶囊的高内化作用，随后是细胞因子分泌和补体激活。体内研究表明，rHBsAg 负载的纳米胶囊在肌肉内或鼻内给药后能够诱导小鼠产生保护水平。总的来说，我们的数据表明，鱼精蛋白纳米胶囊是一种用于改善抗原递呈的创新型热稳定纳米疫苗平台。
