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

小型企业创新研究(SBIR)第一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、国家政府和非营利性疫苗买家节省成本，并使世界上缺乏足够冷链能力的地区能够进入市场。成功开发一种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发的一般方法。这个第一阶段的项目将促进对丝绸-疫苗相互作用的理解，这是指导配方开发所必需的。此外，这些研究还将深入了解丝素蛋白本身的免疫原性，以及丝素对疫苗抗原免疫原性的影响。这项技术具有巨大的商业潜力，因为它可以广泛应用于价值240亿美元的全球市场上的许多新兴和现有疫苗。拟议的项目旨在利用蚕丝的独特特性来满足全球对耐热、耐热疫苗的需求。热不稳定性是疫苗研发中的一个长期问题。尽管努力提高稳定性，但目前的配方方法不允许在环境条件下储存产品。运输和储存期间的温度漂移是常见的，并导致浪费或给药不太理想的疫苗。丝素是一种低成本的生物材料，它的使用代表了疫苗稳定的一种新方法。拟议研究的目标是证明丝绸稳定平台创造一种不需要冷藏的轮状病毒配方的可行性。除了传统的液体和冻干疫苗形式外，还将研究用于口服的可溶解薄膜条的开发。这项拟议的研究将确定热稳定性和免疫原性至少与现有商业配方相当的主要候选丝绸轮状病毒制剂，同时为用丝绸稳定疫苗的更广泛问题提供关键见解。

The broader impact/commercial potential of this Small Business Innovation Research (SBIR) Phase I 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 I project will advance understanding of silk-vaccine interactions, which is needed to guide formulation development. Furthermore, insight into the immunogenicity of silk fibroin itself, as well as the impact of silk on the immunogenicity of a vaccine antigen, will be gained in these studies. 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 demonstrate feasibility of the silk-stabilization platform to create a rotavirus formulation that does not require cold storage. In addition to traditional liquid and lyophilized vaccine formats, development of a dissolvable thin film strip for oral delivery will be investigated. The proposed research will identify lead candidate silk-rotavirus formulations with improved thermostability and immunogenicity that is at least equivalent to the existing commercial formulation, while offering critical insight into broader issues of vaccine stabilization with silk.