I-Corps: Translation potential of an efficient method to generate live-attenuated and replication-defective DNA viruses for vaccine development

这个i-Corps项目的更广泛影响是开发了一种准备病原体(病毒、细菌等)的技术。通过快速、简化、低成本的制造工艺用于疫苗。这项技术对含有DNA的病原体(“DNA病原体”)起作用。这一解决方案前景看好，因为该方法可用于生产针对任何DNA病原体的疫苗，使该技术成为人类和动物健康市场(例如，同伴动物和牲畜)的相关平台。由此产生的疫苗将不需要在运输和储存过程中保持低温，因此将更容易将疫苗运往世界各地。除了病原体可以快速准备好用于疫苗生产外，这一特性还意味着该技术有可能在全球范围内迅速应对流行病和抗击疫苗可预防的疾病。从长远来看，这项技术将被验证为生产细菌疫苗，这对抗菌素耐药性很重要。这项技术应该对研究人员和疫苗制造商有吸引力。这个i-Corps项目利用经验学习和对行业生态系统的第一手调查来评估该技术的翻译潜力。这一解决方案基于一项技术的开发，该技术使用化学物质庆大霉素破坏病原体的DNA，从而产生可用于制造疫苗的减毒活的、复制缺陷的病原体。以前的研究已经纳入了使用人类巨细胞病毒和其他病原体的数据，并证明了经治疗的病原体可以感染细胞，但由于DNA损伤而不能复制。该平台为疫苗行业承诺了两项关键技术创新：1)由于解决方案是DNA病原体不可知的，该技术在所有含有DNA的病原体中都表现出了希望；2)用经庆大霉素处理的病原体生产的疫苗可能不需要冷藏和运输。单是这项创新就将对在世界范围内解决疫苗可预防的疾病具有重大意义。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 of this I-Corps project is the development of a technology that prepares pathogens (viruses, bacteria, etc.) for use in vaccines through a rapid, simplified, low-cost manufacturing process. The technology works on pathogens that contain DNA (“DNA pathogens”). This solution holds promise because the method can be used to generate vaccines against any DNA pathogen, making the technology a platform relevant in both human and animal health markets (e.g., companion animals and livestock). The resulting vaccines will not need to be kept cold during shipping and storage, so it will be easier to get vaccines to places around the world. This attribute, in addition to the rapidity with which pathogens can be readied for vaccine production, means that the technology has the potential to quickly address epidemics and combat vaccine-preventable diseases worldwide. Long term, the technology will be validated to generate bacterial vaccines, important for antibacterial resistance. This technology should be attractive to researchers and vaccine manufacturers.This I-Corps project utilizes experiential learning coupled with a first-hand investigation of the industry ecosystem to assess the translation potential of the technology. This solution is based on the development of a technology that uses the chemical centanamycin to damage the DNA of pathogens and thereby produce live-attenuated, replication-defective pathogens that can be used to make vaccines. Previous studies have incorporated data using human cytomegalovirus and other pathogens and have demonstrated that a treated pathogen can infect cells but not replicate due to damaged DNA. The platform promises two key technical innovations for the vaccine industry: 1) since the solution is DNA pathogen-agnostic, the technique shows promise across all DNA-containing pathogens and 2) vaccines made with centanamycin-treated pathogens may not need cold storage and shipping. This innovation alone would be significant for addressing vaccine-preventable diseases worldwide.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.