RAPID: Scalable Manufacturing of a Microneedle Coronavirus Vaccine Delivery System

这项快速反应研究（RAPID）资助支持有助于新型冠状病毒疫苗输送系统的可扩展制造和纳米技术的研究，资金来自工程局的土木，机械和制造创新部门以及数学和物理科学局的生物材料计划。 目前还没有已知的有效疗法来对抗冠状病毒（COVID 19）疾病，正在开发的疫苗面临着规模和稳定性的制造挑战。这项研究通过将聚合物制造的专业知识与生物医学工程相结合，为疫苗开发带来了先进的纳米制造方法。这种植物病毒为疫苗的发现提供了一种独特的生物材料，因为它可以很容易地被改造成模拟冠状病毒而不具有传染性，并且在各种环境条件下高度稳定。这项技术的创新之处在于，这些候选疫苗可以使用已建立的聚合物加工技术（如注塑成型）制造成自我管理的疫苗贴片，以实现持久的保护性反应。这些可扩展的加工技术可以大规模地影响疫苗的分布，因为它们可以用于以低成本快速制造疫苗/聚合物贴片。该研究是多学科的，涉及聚合物科学，生物工程和植物分子农业。进行这项研究的学生在跨学科的环境中接受培训，使他们处于创新的最前沿，以帮助国家成为技术领导者。主要研究员致力于教育和外展工作，通过让代表性不足的高中生参与研究，并通过公开讲座和演示传播成果。豇豆花叶病毒（CPMV）被用作纳米技术支架，呈现新型冠状病毒的表位（抗原肽），以产生候选疫苗。纳米级病毒样颗粒对免疫系统高度可见，并作为表位呈递技术和佐剂（以增强免疫应答）。这项研究开发了疫苗鸡尾酒，以提供对病毒的最大保护。CPMV特别适用于先进的制造技术。CPMV是通过植物分子农业生产的。基于植物病毒的候选疫苗在递送装置制造所需的聚合物加工温度条件下稳定。随着公共卫生需求的发展，即插即用技术可以迅速改变。例如，如果突变体或新菌株出现，则平台是可适应的，因为表位可以容易地被替换。将CPMV候选疫苗混合到缓慢降解的聚合物中，并注射成型为微针贴片。注塑成型是以低成本制造聚合物器件的可扩展方法。选择聚合物是为了在数月内缓慢释放候选疫苗，在大流行期间提供保护。疫苗的缓慢释放为免疫系统提供了增强，这在单次给药后是有效的。一旦实现，这些补丁可以被运送到冷链之外，并在自我应用时显示出功效。该奖项反映了NSF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。

This Rapid Response Research (RAPID) grant supports research that contributes to the scalable manufacturing and nanotechnology of a novel coronavirus vaccine delivery system with funding from the Civil, Mechanical, and Manufacturing Innovation Division in the Directorate for Engineering and from the Biomaterials Program in the Directorate for Mathematical and Physical Sciences. There are no known effective therapeutics to combat the coronavirus (COVID19) disease and the vaccines in development face manufacturing challenges for scale and stability. This research brings an advanced nanomanufacturing approach to vaccine development by coupling expertise in polymer fabrication with biomedical engineering. The plant virus offers a unique biomaterial for vaccine discovery because it can be easily engineered to mimic coronavirus without being infectious and it is highly stable under various environmental conditions. The innovation in this technology is that these vaccine candidates can be manufactured using established polymer-processing technologies, such as injection molding, into self-administered vaccine patches for durable protective response. These scalable processing technologies can impact vaccine distribution on a massive scale, since they can be used to fabricate vaccine/polymer patches rapidly at low cost. The research is multi-disciplinary and involves polymer science, bioengineering, and plant molecular farming. Students conducting this research are trained in an interdisciplinary environment, putting them at the forefront of innovation to help position the nation as a technological leader. The PIs are committed to education and outreach through engaging underrepresented high school student in research and through dissemination of results via public lectures and demonstrations.Cowpea mosaic virus (CPMV) is used as a nanotechnology scaffold to present epitopes (antigenic peptides) of the novel coronavirus to generate vaccine candidates. The nanoscale virus-like particle is highly visible to the immune system and serves as an epitope presentation technology and adjuvant (to boost the immune response). This research develops vaccine cocktails to provide the most protective shield against the virus. CPMV is especially suited for advanced manufacturing technologies. CPMV is produced through molecular farming in plants. The plant virus-based vaccine candidates are stable under the polymer processing temperature conditions required for delivery device manufacturing. The plug-and-play technology can be quickly changed as public health needs evolve. For example, if mutants or novel strains emerge the platform is adaptable in that the epitopes can be easily replaced. The CPMV vaccine candidates are blended into slowly degradable polymers and injection molded into microneedle patches. Injection molding is a scalable method to manufacture polymeric devices at low cost. The polymers are chosen for slow release of the vaccine candidate over the course of months, providing protection over the course of the pandemic. The slow release of the vaccine provides boosts to the immune system, which is effective after a single administration. Once realized, these patches can be shipped outside of the cold-chain and show efficacy when self-applied.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.