Stabilizing formulations for inhalable powders of an adenovirus 35-vectored tuberculosis (TB) vaccine (AERAS-402)
Stabilizing formulations for inhalable powders of an adenovirus 35-vectored tuberculosis (TB) vaccine (AERAS-402)
复制标题
DOI：
10.1016/j.vaccine.2010.04.059
复制
发表时间：
2010-06-17
期刊：
影响因子：
5.5
通讯作者：
Sadoff, Jerald
中科院分区：
文献类型：
--
作者：
Jin, Tom H.;Tsao, Eric;Sadoff, Jerald
通过喷雾干燥Ad35载体结核AERAS-402疫苗和甘露醇基稳定剂，研制了一种用于气雾剂输送的粉末疫苗。对粉末的热力学性质、吸水率、粒度分布和形貌进行了评价。用组织培养感染剂量(TCID50)测定病毒在喷雾干燥和储存过程中的存活率。甘露醇粉(甘露醇-环糊精-海藻糖-葡聚糖，MCTD)粒度分布窄，平均体积直径3.2~3.5微米(适合人体肺部疫苗接种)，雾化特性好。甘露醇配方产生的喷雾干燥粉末具有疏水性，与吸湿性配方(海藻糖、蔗糖、葡聚糖、PVP、亮氨酸)相比，在4摄氏度、25摄氏度和37摄氏度的生产和储存过程中都有利于病毒的存活。总之，这项研究表明，在一步喷雾干燥过程中，可以生产出适合大规模接种的稳定的结核病疫苗干粉配方。(C)2010爱思唯尔有限公司。保留所有权利。
A powder vaccine intended for aerosol delivery was formulated by spray drying the Ad35-vectored tuberculosis (TB) AERAS-402 vaccine with mannitol-based stabilizers. Thermodynamic properties, water absorption, particle size distribution and morphology of the powders were evaluated. Virus survival during spray drying and storage was determined by medium Tissue Culture Infectious Dose (TCID50). A mannitol-based powder (mannitol-cyclodextrin-trehalose-dextran, MCTD) had a narrow size distribution with a median volume diameter around 3.2-3.5 mu m (suitable for pulmonary vaccination of humans) and good aerosolization characteristics. The spray dry powders generated from mannitol-based formulations were hydrophobic, which benefits virus survival during both production and storage at 4 degrees C, 25 degrees C and 37 degrees C as compared to the hygroscopic formulations (trehalose, sucrose, dextran, PVP, leucine). In conclusion, this study demonstrates that it is possible to produce in a one-step spray drying process a stable dry powder formulation of a TB vaccine suitable for mass vaccination. (C) 2010 Elsevier Ltd. All rights reserved.