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

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.