PROJECT SUMMARY – CORE D: ANIMAL MODELS AND VACCINE EVALUATION Among viruses that cause disease in humans viral zoonoses within the family Paramyxoviridae and order Bunyavirales contain pathogens that cause significant lethality. Importantly, within the Paramyxovirdae the zoonotic henipavirus Hendra virus (HeV) is on the World Health Organizations (WHO) Priority Pathogens list. Notably, henipaviruses stand out for their impressive lethality with case fatality rates averaging about 75%. The Arenaviridae and Phelboviridae families contain viruses that cause severe hemorrhagic disease in humans. These viruses include the arenaviruses Lassa virus (LASV) and Junin virus (JUNV) and the phleboviruses Rift Valley fever virus (RVFV) and severe fever with thrombocytopenia syndrome virus (SFTSV). LASV and RVFV are also included among the WHO List of Priority Pathogens and pose threats to global public health due to the absence of approved vaccines or therapeutics. There is a clear unmet need for medical countermeasures to combat the threat of natural outbreaks, epidemics, or deliberate release. The synergistic activities of the Center partners will be focused on developing novel vaccines, treatments, and tools to support pandemic preparedness. Federal law requires that the paramyxoviruses, arenaviruses, and phleboviruses used in the Center be handled in approved Biosafety Level (BSL)-3 and BSL-4 containment laboratories. Core D provides approved BSL-3/ABSL-3 and BSL-4/ABSL-4 facilities and a trained and highly experienced team of BSL-3 and BSL-4 investigators and staff to perform studies that support Project 2 - 5. The services provided by Core D will include 1) a secure repository of well characterized seed stocks of BSL-3 and BSL-4 paramyxoviruses, arenaviruses, and phleboviruses and know-how to rescue synthetic infectious clones (e.g. Ghana virus, GhV for this U19); 2) in vitro antiviral activity assays; 3) procurement of UTMB IACUC approval of animal protocols; 4) procurement, housing, and husbandry of animals; 5); development and/or optimization of animal models for GhV, Sosuga virus (SOSV) and JUNV to fill gaps where models are needed; 6) virus challenge, treatment, and collection of samples from animals; 7) technical expertise and equipment to conduct clinical pathological, immunological, and virological analysis of samples and to perform necropsies in BSL-3 and BLS-4 containment; 8) histopathological analysis of tissues collected from animals infected with BSL-3 and BSL-4 viruses; and 9) quality systems management of all records and data collected from animal studies. The Animal Models and Vaccine Evaluation Scientific Core (Core D) provides BSL-3 and BSL-4 resources and expertise for Projects 2 – 5. The goal of Core D is to work closely with Research Project and Scientific Core Leaders and staff, the Scientific Advisory Board, and NIAID to advance the development of countermeasures against Paramyxoviridae and Bunyaviridae.