Feasibility study of inhaled hepatitis B vaccine formulated with tetradecylmaltoside.
Feasibility study of inhaled hepatitis B vaccine formulated with tetradecylmaltoside.
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十四烷基麦芽糖苷吸入型乙型肝炎疫苗的可行性研究。
DOI：
10.1002/jps.21069
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发表时间：
2008
影响因子：
3.8
通讯作者：
Ahsan,Fakhrul
中科院分区：
文献类型：
--
作者：
Thomas,Chandan;Rawat,Amit;Bai,Shuhua;Ahsan,Fakhrul
本研究旨在验证以下假设：在啮齿类动物模型中，含有十四烷基-β-麦芽糖苷 (TDM) 的乙型肝炎疫苗配方可增强肺部给药后的免疫反应。市售的重组乙型肝炎疫苗（rHBV）由不同浓度的 TDM 配制而成，并通过气管内注射给麻醉的雄性 Sprague-Dawley 大鼠。以 2 和 4 µg 剂量肌肉注射 rHBV 作为阳性对照。所有制剂均在第 0 天和第 14 天施用，并评估 28 天的免疫反应。通过 ELISA 分析针对 HBsAg 产生的特异性抗体。通过测量支气管肺泡灌洗液（BAL）中碱性磷酸酶（ALP）、乳酸脱氢酶（LDH）和肿瘤坏死因子α（TNF-α）的水平进行安全性研究。当疫苗以 4 µg 剂量肌肉注射时，免疫反应显着增强。当以相同剂量气管内施用普通 rHBV 时，仅观察到免疫反应的适度增加。然而，与通过肺部途径施用的普通 rHBV 相比，4 µg rHBV 加 0.5% TDM 的肺部制剂产生的免疫反应增加了四倍。对于含有 rHBV 加 0.125% 或 0.25% TDM 的制剂，没有观察到免疫反应的增加。 BAL 液中的 ALP 和 LDH 水平表明，乙型肝炎疫苗加 TDM 制剂在首次气管内滴注制剂后会对肺部造成一定损伤；然而，第二次滴注后酶水平往往较低。 TDM 处理的大鼠 BAL 液中 TNF-α 的水平显着低于用阳性对照物质十二烷基硫酸钠处理的大鼠。总体而言，rHBV 与 TDM 配制可增强肺部给药后的免疫反应，rHBV 加 TDM 的肺部配制可作为乙型肝炎疫苗针注射的替代方案。 © 2007 Wiley-Liss, Inc. 和美国药剂师协会 J Pharm Sci 97:1213–1223, 2008
This study was designed to test the hypothesis that formulation of hepatitis B vaccine with tetradecyl‐β‐maltoside (TDM) enhances the immune response after pulmonary administration in a rodent model. Commercially available recombinant hepatitis B vaccine (rHBV) was formulated with varying concentrations of TDM and administered intratracheally to anesthetized male Sprague–Dawley rats. rHBV administered intramuscularly at doses of 2 and 4 µg served as positive controls. All formulations were administered on days 0 and 14 and the immune response was evaluated for 28 days. Specific antibodies generated to HBsAg were analyzed by ELISA. Safety studies were carried out by measuring the levels of alkaline phosphatase (ALP), lactate dehydrogenase (LDH) and tumor necrosis factor α (TNF‐α) in bronchoalveolar lavage (BAL) fluid. There was a significant increase in the immune response when the vaccine was administered intramuscularly at a dose of 4 µg. Only a modest increase in the immune response was observed when plain rHBV was administered intratracheally at the same dose. However, a pulmonary formulation of 4 µg rHBV plus 0.5% TDM produced a fourfold increase in the immune response compared to plain rHBV administered via the pulmonary route. No increase in immune response was observed for formulations containing rHBV plus 0.125% or 0.25% TDM. The levels of ALP and LDH in the BAL fluid suggest that the hepatitis B vaccine plus TDM formulations cause some injury to the lungs after the first intratracheal instillation of the formulation; however, the enzyme levels tended to be lower after the second instillation. The level of TNF‐α in the BAL fluid of TDM‐treated rats was substantially lower than that in rats treated with the positive control substance, sodium dodecyl sulfate. Overall, rHBV formulated with TDM increases the immune response after pulmonary administration, and pulmonary formulation of rHBV plus TDM could be used as an alternative to needle‐based delivery of hepatitis B vaccine. © 2007 Wiley‐Liss, Inc. and the American Pharmacists Association J Pharm Sci 97:1213–1223, 2008