Studies into improved broadly reactive and protective vaccination strategies for high consequence Bunyaviruses

Bunyaviruses represent a large group of viruses, many of which are zoonotic viruses that have important implications for human and animal health. Within this group are several families of viruses that contain high consequence viral species. Notable Bunyaviruses important for human disease include Lassa virus, South American Hemorrhagic fever-causing viruses, Crimean-Congo Hemorrhagic Fever virus, Rift Valley Fever virus, and Hantaviruses, among others. Viruses such as Cache Valley virus, Rift Valley Fever virus, and Schmallenberg virus are among the Bunyaviruses that can cause severe disease in animals, particularly in livestock species with a large economic impact. For this project, we have three specific aims: 1) Computationally design and optimize antigen selection and production for high-consequence Bunyaviruses from different families including Andes virus and Sin Nombre virus (Hantaviruses), different lineages of Lassa virus (Arenavirus), and different lineages of Rift Valley Fever virus (Phenuivirus). This includes both protein-based and viral-vectored vaccine platforms. 2) Evaluate the immunogenicity of vaccine constructs for each virus delivered with different adjuvants and via different routes. 3) Evaluate the effectiveness of selected vaccine candidates in animal models of disease for each virus. Overall, our goal is to take advantage of similarities across viruses within the Bunyavirus class to develop a streamlined approach to rapid vaccine development for emerging and re-emerging Bunyaviruses. Our approach will contribute to faster development of vaccines in the face of emerging pathogens and aid in a critical aspect of epidemic and pandemic preparedness.