Optimization of an alum-adsorbed vaccine powder formulation for epidermal powder immunization
Optimization of an alum-adsorbed vaccine powder formulation for epidermal powder immunization
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DOI：
10.1023/a:1024493719236
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发表时间：
2003-07-01
影响因子：
3.7
通讯作者：
Chen, DX
中科院分区：
文献类型：
--
作者：
Maa, YF;Shu, C;Chen, DX
目的。开发稳定有效的铝盐（明矾）吸附疫苗粉末制剂，用于通过喷雾冷冻干燥（SFD）工艺进行表皮粉末免疫（EPI）。方法。使用粒度分析、振实密度和扫描电子显微镜测定粉末特性。通过光学显微镜和颗粒沉降监测明矾凝结。蛋白质分析通过 BCA 蛋白质测定、SDS-PAGE 和酶免疫测定进行测定。分别对无毛豚鼠和猪进行体内免疫原性和皮肤反应原性测试。结果。使用海藻糖/甘露醇/右旋糖酐组合赋形剂将乙型肝炎表面抗原（HBsAg）吸附到氢氧化铝或磷酸铝上进行SFD制备，生产出颗粒致密、粉末流动性和吸湿性令人满意的疫苗粉末。该配方还为粉末和抗原提供了出色的长期稳定性。影响明矾颗粒凝结的两个最重要的因素是冷冻速率和 SFD 液体配方中铝的浓度。 SFD 疫苗通过 EPI 递送至无毛豚鼠或重构后肌肉注射时，与原始液体疫苗具有相同的免疫原性。进一步的研究表明，EPI与SFD明矾吸附白喉-破伤风类毒素疫苗的耐受性良好，而液体制剂的针注射会引起持续性肉芽肿。结论。 SFD 对明矾吸附疫苗的稳定性对于将疫苗接种扩展到缺乏运输和储存冷链的地区具有重要意义，也可能加速 EPI 等新免疫技术的开发。
Purpose. To develop stable and effective aluminum salt (alum)-adsorbed vaccine powder formulations for epidermal powder immunization (EPI) via a spray freeze-drying (SFD) process.Methods. Powder properties were determined using particle size analysis, tap density, and scanning electron microscopy. Alum coagulation was monitored via optical microscopy and particle sedimentation. Protein analysis was determined by the BCA protein assay, SDS-PAGE, and an enzyme immunoassay. In vivo immunogenicity and skin reactogenicity were performed on hairless guinea pigs and pigs, respectively.Results. SFD of hepatitis B surface antigen (HBsAg) adsorbed to aluminum hydroxide or aluminum phosphate using an excipient combination of trehalose/mannitol/dextran produced vaccine powders of dense particles and satisfactory powder flowability and hygroscopicity. This formulation also offered excellent long-term stability to the powder and the antigen. The two most important factors influencing alum particle coagulation are the freezing rate and the concentration of aluminum in the liquid formulation for SFD. The SFD vaccines, when delivered to hairless guinea pigs by EPI or injected intramuscularly after reconstitution, were as immunogenic as the original liquid vaccine. A further study showed that EPI with SFD alum-adsorbed diphtheria-tetanus toxoid vaccine was well tolerated, whereas needle injection of the liquid formulation caused persistent granuloma.Conclusions. Stabilization of alum-adsorbed vaccine by SFD has important implications in extending vaccination to areas lacking a cold chain for transportation and storage and may also accelerate the development of new immunization technologies such as EPI.