Novartis Vaccines and Diagnostics, 350 Massachusetts Avenue, Cambridge, MA-02139, United States.
Vaccine. 2013 Jul 25;31(34):3435-41. doi: 10.1016/j.vaccine.2013.01.050. Epub 2013 Feb 8.
Delivery of influenza vaccine using innovative approaches such as microneedles has been researched extensively in the past decade. In this study we present concentration followed by formulation and coating of monobulks from 2008/2009 seasonal vaccine on to 3M's solid microstructured transdermal system (sMTS) by a GMP-scalable process. The hemagglutinin (HA) in monobulks was concentrated by tangential flow filtration (TFF) to achieve HA concentrations as high as 20mg/ml. The stability of the coated antigens was evaluated by the functional assay, single radial immunodiffusion (SRID). The data generated show stability of the coated antigen upon storage at 4°C and room temperature in the presence of desiccant for at least 8 weeks. Freeze-thaw stability data indicate the stability of the coated antigen in stressed conditions. The vaccine coated microstructures were evaluated in vivo in a guinea pig model, and resulted in immune titers comparable to the traditional trivalent vaccine administered intramuscularly. The data presented indicate the potential use of the technology in delivery of influenza vaccine. This paper also addresses the key issues of stability of coated antigen, reproducibility and scalability of the processes used in preparation of influenza vaccine coated microneedle patches that are important in developing a successful product.
在过去的十年中，人们广泛研究了使用创新方法（如微针）来递送流感疫苗。在本研究中，我们通过符合 GMP 标准的可扩展工艺，将 2008/2009 季节性疫苗的单块从浓度到配方再到 3M 的固体微结构透皮系统（sMTS）的包衣进行了研究。单块中的血凝素（HA）通过切向流过滤（TFF）浓缩，达到高达 20mg/ml 的 HA 浓度。通过功能测定（单扩散免疫测定）评估包被抗原的稳定性。所生成的数据表明，在干燥剂存在的情况下，包被抗原在 4°C 和室温下储存至少 8 周时稳定。冻融稳定性数据表明在应激条件下包被抗原的稳定性。在豚鼠模型中评估了包被微结构的体内效果，结果表明其免疫效价可与肌肉内注射的传统三价疫苗相媲美。所提供的数据表明该技术在流感疫苗的递送上具有潜在的应用价值。本文还解决了包被抗原稳定性、涂层流感疫苗微针贴片制备过程的重现性和可扩展性等关键问题，这些问题对于开发成功的产品非常重要。
