SBIR Phase II: A New Approach to Developing a Heat-stable Rotavirus Vaccine

这一小企业创新研究（SBIR）第二阶段项目的更广泛影响/商业潜力将是增加全球获得疫苗的机会，并降低与传染病相关的死亡率。例如，轮状病毒是幼儿严重胃肠炎的主要原因，缺乏疫苗接种每年导致45万人死亡。耐热轮状病毒疫苗将为疫苗制造商、国家政府和非营利疫苗购买者节省成本，并使世界上缺乏足够冷链能力的地区能够进入市场。成功开发稳定的轮状病毒疫苗不仅将对全球轮状病毒免疫工作产生重大积极影响，而且还可能彻底改变疫苗交付和分配的一般方法。该第二阶段项目将推进一种新的平台技术的商业化，该技术既能稳定疫苗，又能实现新的输送形式。这项技术具有巨大的商业潜力，因为它可以广泛应用于240亿美元全球市场中的许多新兴和现有疫苗。该项目旨在利用蚕丝的独特特性来满足全球对耐用、耐热疫苗的需求。热不稳定性是疫苗开发中的一个长期问题。尽管努力提高稳定性，但目前的制剂方法不允许产品在环境条件下储存。运输和储存期间的温度偏移是常见的，并导致浪费或接种次优疫苗。丝素蛋白是一种低成本的生物材料，它的使用代表了一种新的疫苗稳定方法。拟议研究的目标是推动丝稳定平台实现不需要冷藏的疫苗的商业化。在成功的I期结果的基础上，先进的配方优化研究将确定轮状病毒的最终产品配方，该配方与规模化生产相容，并实现商业产品所需的所有储存和体内属性。通过工艺优化研究，用于口服递送轮状病毒的可溶性薄条的制造将转化为可扩展的制造工艺，该工艺为传统干燥方法提供了有吸引力的替代方案。在改进的动物模型中评价稳定的轮状病毒疫苗膜将能够验证体内免疫原性，并提供更广泛的疫苗稳定性和口服膜递送的见解。

The broader impact/commercial potential of this Small Business Innovation Research (SBIR) Phase II project will be to increase global access to vaccines and reduce mortality associated with infectious diseases. As an example, Rotavirus is a major cause of severe gastroenteritis among young children and lack of vaccination results in 450,000 deaths annually. A thermostable rotavirus vaccine would create cost-savings for vaccine manufacturers, national governments, and non-profit vaccine buyers and enable market access in areas of the world that lack sufficient cold-chain capacity. Successful development of a stable rotavirus vaccine would not only have significant positive impact on global rotavirus immunization efforts, but may also revolutionize the general approach to vaccine delivery and distribution. This Phase II project will advance towards commercialization a novel platform technology that both stabilizes vaccines and enables novel delivery formats. This technology has significant commercial potential in that it can be broadly applied to numerous emerging and existing vaccines in the $24 Billion global market. The proposed project seeks to leverage the unique properties of silk to meet the global need for robust, thermostable vaccines. Thermal instability is a long-standing problem in vaccine development. Despite efforts to improve stability, current formulation approaches do not allow product storage under ambient conditions. Temperature excursions during shipment and storage are common and result in wastage or administration of suboptimal vaccines. The use of silk fibroin, a low-cost biomaterial, represents a novel approach to vaccine stabilization. The goal of the proposed research is to advance the silk-stabilization platform towards commercialization of vaccines that do not require cold storage. Building upon successful Phase I results, advanced formulation optimization studies will define a final product formulation for rotavirus that is compatible with scaled manufacturing and achieves all storage and in vivo attributes necessary for a commercial product. Through process optimization studies, fabrication of a dissolvable thin strip for oral delivery of rotavirus will be translated into a scalable manufacturing process that provides an attractive alternative to traditional drying methods. Evaluation of stabilized rotavirus vaccine films in an improved animal model will enable validation of in vivo immunogenicity and offer insight into vaccine stabilization and oral film delivery more broadly.