University of Groningen, Department of Pharmaceutical Technology and Biopharmacy, Antonius Deusinglaan 1, 9713AV Groningen, The Netherlands.
Institute for Translational Vaccinology (Intravacc), P.O. Box 450, 3720 AL Bilthoven, The Netherlands.
Eur J Pharm Sci. 2014 May 13;55:36-45. doi: 10.1016/j.ejps.2014.01.005. Epub 2014 Jan 25.
The current hepatitis B vaccines need to be stored and transported under refrigerated conditions (2-8°C). This dependence on a cold-chain is highly challenging in areas where hepatitis B virus infections are endemic. To decrease the cold-chain dependency, powder formulations of the hepatitis B surface antigen (HBsAg) without aluminum were prepared by spray-freeze drying in the presence of either inulin or a combination of dextran and trehalose. The stability of HBsAg in the amorphous powder formulations was strongly improved during storage both at room temperature and at an elevated temperature (60°C), compared to a liquid plain and an aluminum hydroxide adjuvanted HBsAg formulation. Immunogenicity studies in mice showed that reconstituted powder formulations induced higher IgG immune responses after intramuscular administration than those induced after administration of unprocessed plain antigen. Although the immune response was not as high as after administration of aluminum adjuvanted HBsAg, the immune response to the reconstituted vaccines shifted towards a more balanced Th1/Th2 response compared to the aluminum containing HBsAg formulation.
当前的乙型肝炎疫苗需要在冷藏条件（2-8°C）下储存和运输。在乙型肝炎病毒感染流行的地区，这种对冷链的依赖极具挑战性。为了减少对冷链的依赖，通过喷雾冷冻干燥，在存在菊粉或右旋糖酐和海藻糖的组合的情况下，制备了不含铝的乙型肝炎表面抗原（HBsAg）的粉末制剂。与液体普通制剂和含氢氧化铝佐剂的 HBsAg 制剂相比，HBsAg 在无定形粉末制剂中的稳定性在室温下和高温（60°C）下的储存期间得到了极大的提高。在小鼠中的免疫原性研究表明，与未经处理的普通抗原给药相比，肌肉内给药后复溶的粉末制剂诱导更高的 IgG 免疫应答。尽管免疫应答不如铝佐剂 HBsAg 给药后那么高，但与含铝的 HBsAg 制剂相比，复溶疫苗的免疫应答向更平衡的 Th1/Th2 应答转移。
