Stable dry powder formulation for nasal delivery of anthrax vaccine.
Stable dry powder formulation for nasal delivery of anthrax vaccine.
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DOI：
10.1002/jps.22742
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发表时间：
2012-01
影响因子：
3.8
通讯作者：
Hickey, Anthony J.
中科院分区：
文献类型：
--
作者：
Wang, Sheena H.;Kirwan, Shaun M.;Abraham, Soman N.;Staats, Herman F.;Hickey, Anthony J.
关键词：
目前，生物防御对防止炭疽病很感兴趣。在这里我们研制出了新一代稳定有效的炭疽疫苗。我们研究了rPA与一种新的粘膜佐剂，肥大细胞激活剂化合物48/80鼻内递送引起的免疫应答。在优化条件下，通过喷雾冷冻干燥（SFD）制备粉末形式的疫苗制剂，以产生目标尺寸为D50=25μm的颗粒，适用于递送至家兔鼻腔。对粉末疫苗的理化性质进行表征，以评估其递送和储存潜力。通过CD和ATR-FTIR证实rPA的结构稳定性，而通过基于细胞的测定监测rPA和C48/80的功能稳定性。使用用于直接鼻腔应用的单位剂量粉末装置进行动物研究。结果表明，C48/80在家兔体内具有有效的粘膜佐剂活性。新鲜制备的SFD粉末疫苗制剂或在室温下储存超过两年的粉末引起显著升高的血清PA特异性和致死毒素中和抗体滴度，其与用rPA IM免疫诱导的滴度相当。这种疫苗制剂的鼻腔给药可能是目前许可的疫苗的可行替代方案，或者是其他粘膜传播疾病的有吸引力的疫苗平台。
There is a current biodefense interest in protection against Anthrax. Here we developed a new generation of stable and effective anthrax vaccine. We studied the immune response elicited by rPA delivered intranasally with a novel mucosal adjuvant, a mast cell activator Compound 48/80. The vaccine formulation was prepared in a powder form by spray-freeze-drying (SFD) under optimized conditions to produce particles with a target size of D50=25μm, suitable for delivery to the rabbit nasal cavity. Physicochemical properties of the powder vaccines were characterized to assess their delivery and storage potential. Structural stability of rPA was confirmed by CD and ATR-FTIR, while functional stability of rPA and C48/80 was monitored by cell-based assays. Animal study was performed using a unitdose powder device for direct nasal application. Results showed that C48/80 provided effective mucosal adjuvant activity in rabbits. Freshly prepared SFD powder vaccine formulations or powders stored for over two years at room temperature elicited significantly elevated serum PA-specific and lethal toxin neutralization antibody titers that were comparable to that induced by IM immunization with rPA. Nasal delivery of this vaccine formulation may be a viable alternative to the currently licensed vaccine, or an attractive vaccine platform for other mucosally transmitted diseases.
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