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

这个小企业创新研究（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有关的死亡率。例如，轮状病毒是幼儿严重肠胃炎的一个主要原因，由于缺乏疫苗接种，每年造成45万人死亡。耐热轮状病毒疫苗将为疫苗制造商、各国政府和非营利性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。成功研制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的积极影响，而且还可能彻底改变疫苗提供和分发的一般方法。这个第一阶段项目将促进对丝质疫苗相互作用的理解，这是指导配方开发所必需的。此外，深入了解丝素蛋白本身的免疫原性，以及丝对疫苗抗原免疫原性的影响，将在这些研究中获得。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。拟议的项目寻求利用丝绸的独特特性来满足全球对强大的、耐热的疫苗的需求。热不稳定性是疫苗研制中的一个长期问题。尽管努力提高稳定性，目前的配方方法不允许产品在环境条件下储存。在运输和储存过程中的温度偏差是常见的，并导致浪费或施用不理想的疫苗。丝素蛋白是一种低成本的生物材料，它的使用代表了一种稳定疫苗的新方法。拟议研究的目标是证明丝绸稳定平台创建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格式外，还将研究用于口服递送的可溶解薄膜条的开发。拟议的研究将确定具有改进的热稳定性和免疫原性的候选丝绸轮状病毒配方，至少相当于现有的商业配方，同时为丝绸疫苗稳定性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.