VacciRAPTOR: High-throughput, Continuous Flow-through Device for Psoralen-UVA Inactivation of Dengue Virus

Dengue virus is a mosquito-transmitted pathogen that is a significant global health concern, affecting millions annually and causing severe disease and death. The limitations of current Dengue vaccines necessitate innovate approaches to vaccine development. This proposal introduces a novel solution: PsoraVAX-DEN, an inactivated vaccine that harnesses the unique advantages provided by pathogen inactivation with UV light in an industrialized, continuous flow format to rapidly produce safe and effective vaccines for Dengue at a scale that meets increasing global demand.   The VacciRAPTORTM technology, developed by the Rapid Prototyping Laboratory at Colorado State University and optioned to Solaris Vaccines, facilitates high-throughput inactivation resulting in efficient, large-scale vaccine production. The system is designed to precisely control the intensity and duration of exposure to specific wavelengths of UV light in the presence of photosensitizing chemicals, such as the flavin psoralen. This results in the ideal balance between disrupting pathogen genetic material while preserving key antigen structures. Advantages of this approach include continuous flow for high-throughput inactivation, enhanced antigen preservation, potential for multivalent vaccine formulations, low-cost vaccine production, and the facilitation of local manufacturing to support global health needs. Our goal is to apply this innovate approach to the production of an inactivated Dengue vaccine.   Technical objectives include:    1. Developing the VacciRAPTOR for psoralen/UV-A inactivation of up to 5L of Dengue virus. This includes converting the light source from UV-B to UV-A, improving the reactor coil set-up, and characterizing the system.    2. Inactivate Dengue virus using psoralen/UV-A with the VacciRAPTOR device. This includes validating VacciRAPTOR’s effectiveness across  Dengue serotypes 1-4 . The effects of flow rate, irradiation time, and energy dose on inactivation will be optimized to reach complete inactivation, which will be confirmed by cytopathic effect, immunofluorescence, and plaque assay.    A successful outcome from Phase I will mark a significant milestone in the development of PsoraVAX-DEN, paving the way for scaling production volumes up to 50 L in Phase II. Ultimately, this project will result in a validated high-throughput device that can accommodate different pathogens and volume scales for rapid vaccine production. Additionally, steps will be taken to certify the VacciRAPTOR for cGMP manufacturing and BSL3/BSL4 compatibility. The success of this project will demonstrate rapid and responsive vaccine development against emerging pathogen threats that will protect both military and civilian populations globally.