STTR Phase I: A platform to overcome immunodominance in vaccine development

The broader impact/commercial potential of this Small Business Technology Transfer (STTR) Phase I project is to advance a novel vaccine platform to develop engineered vaccines that provide longer lasting protection against infectious diseases. Several current vaccines face challenges in reliably protecting populations against rapidly evolving pathogens where prior exposure negatively impacts vaccine effectiveness. This project develops an innovative approach aimed at boosting the immune response to critical parts of pathogens, overcoming limitations associated with previous exposures or immune system biases. By directing immune responses toward conserved, essential regions of pathogens, the innovation has significant commercial and societal potential, including the development of vaccines that are effective across multiple pathogen variants. As an initial area of translation, the technology will be applied toward prevention of healthcare-associated infections caused by antibiotic-resistant bacteria. This approach addresses an unmet clinical need and offers healthcare systems substantial cost savings and improved patient outcomes. The market opportunity for such vaccines is substantial, with potential annual revenues exceeding $200 million by the third year of commercial production. The resulting technology and its applications could provide durable competitive advantages through enhanced vaccine effectiveness, positioning it as a key factor in enabling commercial success and improving public health. This Small Business Technology Transfer (STTR) Phase I project aims to overcome a significant limitation in vaccine development known as immune imprinting, which occurs when prior exposure to pathogens biases immune responses away from protective targets. The objective is to utilize a novel method involving engineered antigens containing chemically modified amino acids to enhance immune recognition and stimulate targeted protective responses. The research goals are to validate computational methods for accurately predicting optimal sites for antigen modifications, demonstrate increased antibody production specifically targeting essential pathogen regions, and confirm that these improvements enhance cross-strain protection. Research activities will include computational modeling to predict antigen modification sites, genetic engineering techniques to produce modified vaccine candidates, and immunological studies in animal models to evaluate effectiveness. Anticipated technical outcomes include validated predictive tools that significantly reduce experimental trial-and-error, proof-of-concept demonstration of enhanced antibody responses toward targeted regions of antigens, and improved vaccine induced protection in animal models. 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.