Design and testing picornavirus vaccine candidates

PROJECT SUMMARY – RP1 Design and testing of picornavirus vaccine candidates The need for effective vaccines against enteroviruses and rhinoviruses cannot be overstated. Given the ever- increasing threat of these viral infections and their associated health impacts, it is crucial to develop a general

platform for rapid vaccine development. With this medical need in mind, here we propose to create such a platform, one that can be easily and quickly adapted to different strains of the viruses as they emerge. We envision a system that combines the latest tools and technologies, including new developments in molecular

biology, immunology, and vaccine design, to accelerate the discovery and development of new candidate vaccines. By doing so, we mill make meaningful contributions towards protecting global populations from the devastating effects of these viruses. Our general approach is to design immunogens that will provide effective protection against these viruses,

incorporating information about sites of vulnerability for protective human monoclonal antibodies (mAbs) (discovered in Research Project 2, focused on human mAbs). This effort is a crucial undertaking, as the five human pathogens prototypes on which we will focus - Rhinovirus C, Enteroviruses A71 and D68, Coxsackievirus

B3 and Echovirus 11, are among the most medically significant viruses causing respiratory, gastrointestinal, and nervous system diseases on a global scale. The innovative candidate vaccine platforms we will deploy are designed with multiple technical advances, especially structurally-stabilized virus-like particles (VLPs) that

can be used as protein- or nucleic-acid-based immunogens. By leveraging the knowledge the BP4 consortium obtains from detailed structure-function studies of protective human monoclonal antibodies, we can develop new candidate vaccines that induce protection from pathogenic picornaviruses and reduce the risk of dangerous

outbreaks. In addition, we will combine these immunogens with a self-replicative RNA-based mucosal adjuvant. This novel adjuvant mimics the effects of virus infection and triggers innate local immune responses, ensuring robust T-cell and B-cell adaptive immune responses and long-lasting protection. By generating both systemic

and mucosal immune responses, we aim to create a robust defense against these viruses. In the context of these studies, we will also develop new animal models to optimize testing of novel vaccination strategies and to examine the immunogenicity and protection elicited by our candidate vaccines. The lead

vaccines will be advanced with an extensive network of industry and non-profit partners.