Maa Yuh-Fun, Shu Cassandra, Ameri Mahmoud, Zuleger Cindy, Che Jenny, Osorio Jorge E, Payne Lendon G, Chen Dexiang
PowderJect Vaccines, Inc., Madison, Wisconsin 53711, USA.
Pharm Res. 2003 Jul;20(7):969-77. doi: 10.1023/a:1024493719236.
To develop stable and effective aluminum salt (alum)-adsorbed vaccine powder formulations for epidermal powder immunization (EPI) via a spray freeze-drying (SFD) process.
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.
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.
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.
通过喷雾冷冻干燥（SFD）工艺开发用于表皮粉末免疫（EPI）的稳定且有效的铝盐（明矾）吸附疫苗粉末制剂。
使用粒度分析、振实密度和扫描电子显微镜测定粉末性质。通过光学显微镜和颗粒沉降监测明矾凝聚。通过BCA蛋白质测定、SDS-PAGE和酶免疫测定进行蛋白质分析。分别在无毛豚鼠和猪身上进行体内免疫原性和皮肤反应原性研究。
使用海藻糖/甘露醇/右旋糖酐的辅料组合对吸附于氢氧化铝或磷酸铝的乙型肝炎表面抗原（HBsAg）进行SFD，制得的疫苗粉末颗粒致密，具有令人满意的粉末流动性和吸湿性。该制剂还为粉末和抗原提供了出色的长期稳定性。影响明矾颗粒凝聚的两个最重要因素是冷冻速率和SFD液体制剂中铝的浓度。通过EPI将SFD疫苗递送至无毛豚鼠或复溶后肌肉注射时，其免疫原性与原始液体疫苗相同。进一步的研究表明，用SFD明矾吸附的白喉-破伤风类毒素疫苗进行EPI耐受性良好，而注射该液体制剂会导致持续性肉芽肿。
通过SFD稳定明矾吸附疫苗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，并且还可能加速诸如EPI等新免疫技术的发展。
