Self-adjuvanting Vaccine Platform

About

Introduction: Virus-like particles (VLPs) are an often-explored vaccine platform that can provide a safe and effective alternative to traditional live virus-based vaccines. VLP vaccines have demonstrated effectiveness against several viruses such as Hepatitis B and Human Papillomavirus. Replication incompetence and consistency of production make them safe to use in immunocompromised populations and easy to commercialize. However, VLP immunogenicity is weak compared to live virus-based vaccines, requiring multiple immunizations and an adjuvant to elicit robust immunity. Improvement of VLP immunogenicity while maintaining the safety profile would represent a welcome advancement, especially where ring vaccination strategies are used such as with Ebola virus (EBOV). With this invention, investigators engineered a VLP vaccine platform with remarkably enhanced immunogenicity even without an adjuvant and have demonstrated proof-of-principle for this platform with EBOV VLPs (eVLPs). Technology: Georgia State University inventors developed a VLP technology that is self-adjuvanting, resulting in a vaccine platform that was shown with in vitro studies to generate robust immunity with a single dose. EBOV was taken as the initial target. By incorporating two CARD Type I Interferon (IFN)-inducing domains (from the RIG-I gene) into the Ebola NP protein and co-expressing this with Ebola GP and VP40, self-adjuvanting eVLPs were created. CARD domains are known to strongly induce the IFN signaling pathway against viral infections or tumor cells. Initial in vitro studies demonstrated that eVLPs trigger robust dendritic cell stimulation and elicit significantly enhanced anti-EBOV GP antibody responses compared to standard VLPs and do so after a single immunization without any adjuvant. This new VLP vaccine platform is modular, easily adaptable to other pathogenic targets, and provides potent immunogenicity while maintaining the positive safety profile of a VLP vaccine.