University of Strathclyde, Strathclyde Institute of Pharmacy and Biomedical Science, 27 Taylor Street, Glasgow G4 0NR, UK.
Methods. 2009 Dec;49(4):322-7. doi: 10.1016/j.ymeth.2009.04.015. Epub 2009 May 4.
Oral vaccination using protein antigens is complicated by the degradative effects of the inhospitable conditions in the gastrointestinal tract, such as low pH and digestive enzymes, nescessitating protection and effective delivery of the antigen. The bilosome is a lipid-based, vesicle delivery system incorporating bile salts, which is believed to protect the antigen from degradation, and has been shown to induce significant antibody responses when delivered orally with various vaccines. In translational research, from laboratory bench to industrial scale-up, it is necessary to optimise the manufacturing process in order to improve efficiency and simplify production, giving a more economical end-product. In this study we tested two simplified production methods (3-step and 1-step) along with two different storage methods (lyophilised and non-lyophilised), as well as looking at the effect of buffer pH. The formulations were assessed in a murine system for immunogenicity, alongside characterisation in terms of size and antigen entrapment, with the stability of these aspects assessed with respect to time. Both lyophilised and non-lyophilised 3-step formulations induced significant IgG1, IgG2a and IgA titres, with the lyophilised version showing stable size and antigen entrapment up to 9months.
口服疫苗接种使用蛋白质抗原，由于胃肠道内环境恶劣，存在低 pH 值和消化酶等因素，会导致抗原降解，因此需要保护和有效递送抗原。双分子层体是一种基于脂质的囊泡递药系统，包含胆盐，据信它可以保护抗原免受降解，并已被证明在与各种疫苗联合口服给药时可诱导显著的抗体应答。在从实验室到工业规模的转化研究中，需要优化制造工艺，以提高效率并简化生产，从而获得更经济的最终产品。在这项研究中，我们测试了两种简化的生产方法（三步法和一步法）以及两种不同的储存方法（冻干和非冻干），并研究了缓冲液 pH 值的影响。我们在小鼠系统中评估了这些配方的免疫原性，并从大小和抗原包封的角度进行了特征描述，同时还评估了这些方面随时间的稳定性。冻干和非冻干的三步法配方均能诱导显著的 IgG1、IgG2a 和 IgA 效价，冻干版本的大小和抗原包封稳定，可长达 9 个月。
