SBIR Phase I: Development of an oral recombinant subunit vaccine to protect against COVID-19

这个小企业创新研究第一阶段项目的更广泛的影响/商业潜力是为新冠肺炎开发一种新的自我管理的疫苗，使用一种新的口服给药平台。该项目将开发一种产生强烈免疫反应的新技术。它可用于制定和评估许多疾病的潜在疫苗，有力地支持公共卫生。这项小型企业创新研究(SBIR)第一阶段项目建议开发一种针对SARS-CoV-2的口服重组亚单位疫苗。这将通过将C型凝集素受体激动剂(甘露聚糖)和靶抗原(刺突蛋白的受体结合域亚单位)吸附到铝佐剂上，然后进行肠内微胶囊口服和喷雾干燥来实现。该平台已被证明成功地诱导了黏膜免疫反应，这是理想的保护，以抵御SARS-CoV-2，通过粘膜表面进入。该项目还将通过进一步开发分析分析方法和优化喷雾干燥工艺来帮助推进该技术。靶抗原RBD的生物物理表征和制剂的开发，将首先进行，以实现良好的抗原物理稳定性。然后，对干粉工艺进行了研究和优化。干粉的稳定性将在体外通过颗粒大小、酶联免疫吸附试验、高温加速稳定性和体内小鼠免疫原性研究进行分析，以进一步了解制造工艺及其对疫苗稳定性和效力的影响。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

The broader impact/commercial potential of this Small Business Innovation Research (SBIR) Phase I project is to develop a new self-administered vaccine for COVID-19 using a novel oral delivery platform. This project will develop a new technique to generate a strong immune response. It can be used in formulating and evaluating potential vaccines for many diseases, strongly supporting public health. This Small Business Innovation Research (SBIR) Phase I project proposes to develop an orally administered recombinant subunit vaccine targeting SARS-CoV-2. This will be achieved by adsorbing C-type lectin receptor agonist (mannan) and the target antigen (receptor binding domain subunit of spike protein) to aluminum adjuvant, followed by enteric microencapsulation for oral delivery, and spray drying. This platform has been shown to successfully induce mucosal immune response, which is ideal to protect against SARS-CoV-2, which enters via mucosal surfaces. This project will also help advance the technology by further developing analytical assays and optimizing the spray drying processes. Biophysical characterization of the target antigen RBD and formulation development and will first be conducted to achieve good antigen physical stability. Then, dried powder processes will be investigated and optimized. The stability of the dried powders will be analyzed in vitro by particle size, ELISA, during accelerated stability at high temperatures, and in vivo in mouse immunogenicity studies, to further understand the manufacturing process and its impact on vaccine stability and potency.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.