SBIR Phase I: At home, single dose mRNA vaccine patch (COVID-19)

这项小企业创新研究（SBIR）第一阶段项目的更广泛影响/商业潜力将是为COVID-19大流行提供一种新的疫苗。迄今为止，已有数百万人感染，数十万人死亡。临床试验中的主要候选疫苗需要两剂，导致：1)由于缺乏隔离而增加传播，或2)由于不遵守规定而不完全接种。成功开发单剂自涂疫苗不仅将对全球COVID-19免疫工作产生重大积极影响，而且还可能改变疫苗交付和分发的一般方法。该项目促进了人们对使用一种新型家庭设备作为多种疾病疫苗接种工具的理解，广泛地促进了公共卫生。这项小企业创新研究（SBIR）一期项目旨在将基于丝绸的微针贴片与mrna -脂质纳米颗粒（LNP）结构相结合，以满足全球对强效COVID-19疫苗的需求。将丝素蛋白（一种低成本生物材料）的独特特性与单剂量自涂微针贴片相结合，代表了一种新的疫苗接种方法，并将通过允许目标抗原在两周内缓慢释放来提高保护效果。此外，使用mRNA编码SARS-CoV-2肽，产生针对刺突蛋白的中和抗体，并减轻抗体依赖性增强的潜在问题，最终将产生更安全、更有效的疫苗。拟议研究的目标是证明丝- mrna - lnp复合物的领先配方，该复合物将具有热稳定性，并确定目标抗原的释放谱，以提高SARS-CoV-2的免疫原性。初步的体外配方筛选和体内剂量和计划的结果将用于开发丝微针贴片的配方，用于二期研究。该项目将确定主要候选丝绸- mrna - lnp货架稳定配方，其免疫原性至少相当于传统的非配方注射剂，同时为基于mrna的疫苗接种和持续释放的更广泛影响提供重要见解。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 will be to provide a new vaccine for the COVID-19 pandemic. To date millions have been infected, with hundreds of thousands of deaths. Leading vaccine candidates in clinical trials require two doses, resulting in either: 1) increased spread due to lack of isolation, or 2) incomplete vaccination due to non-compliance. Successful development of a single-dose, self-applied vaccine would not only have a significant positive impact on global COVID-19 immunization efforts, but may also trasnsform the general approach to vaccine delivery and distribution. This project advances the understanding of using a novel at-home device as a vaccination tool for many diseases, broadly aiding public health.This Small Business Innovation Research (SBIR) Phase I project seeks to combine a silk-based microneedle patch with an mRNA-lipid nanoparticle (LNP) construct to meet the global need for a robust COVID-19 vaccine. Combining the unique properties of silk fibroin, a low-cost biomaterial, with a single-dose, self-applied microneedle patch represents a novel approach to vaccination and will result in improved protection by allowing the target antigen to slowly release over two weeks. Additionally, the use of mRNA encoding SARS-CoV-2 peptides that produce neutralizing antibodies against the spike protein and mitigate potential issues from antibody-dependent enhancement will ultimately result in a safer and more effective vaccine. The goal of the proposed research is to demonstrate lead formulations of a silk-mRNA-LNP complex that will be thermally stable and identify a release profile of target antigen to improve SARS-CoV-2 immunogenicity. Results from preliminary in vitro formulation screens and in vivo dosing and scheduling will be used to develop the formulations for the silk microneedle patch in Phase II studies. This project will identify lead candidate silk-mRNA-LNP shelf-stable formulations with improved immunogenicity that is at least equivalent to traditional, non-formulated injections, while offering critical insight into broader implications of mRNA-based vaccinations and sustained release.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.