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

这项小企业创新研究（SBIR）第一阶段项目的更广泛影响/商业潜力是利用一种新型口服给药平台开发一种新的COVID-19自我给药疫苗。这个项目将开发一种新技术来产生强烈的免疫反应。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。这个小企业创新研究（SBIR）第一阶段项目提议开发一种针对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（刺突蛋白受体结合域亚基）吸附到铝佐剂上，然后通过肠微胶囊口服给药，然后喷雾干燥来实现。该平台已被证明可以成功诱导粘膜免疫反应，这是防止通过粘膜表面进入的SARS-CoV-2的理想选择。该项目还将通过进一步发展分析分析和优化喷雾干燥过程来帮助推进该技术。靶抗原RBD的生物物理特性和制剂的研制将首先进行，以达到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。干粉的稳定性将通过体外粒度、ELISA、高温加速稳定性和小鼠体内免疫原性研究进行分析，以进一步了解生产工艺及其对疫苗稳定性和效力的影响。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值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.