PROJECT SUMMARY/ABSTRACT – Core E (Animal Model Development and Preclinical Evaluation) Among viruses that cause disease in humans, viral zoonoses within the family Paramyxoviridae and order Bunyavirales contain pathogens that cause significant lethality. Importantly, the Arenaviridae and Nairoviridae families contain viruses that cause severe hemorrhagic disease in humans. These viruses include the arenaviruses Lassa, Machupo, Lujo, and Chapare, and the nairovirus Crimean-Congo hemorrhagic fever virus. All of these viruses are also included among the World Health Organization’s (WHO) List of Priority Pathogens. Within the Paramyxovirdae, the zoonotic henipaviruses Hendra virus and Nipah virus (NiV) are also on the WHO Priority Pathogens list. Notably, these henipaviruses stand out for their impressive lethality with case fatality rates averaging about 75%. Significantly, there is evidence of multiple rounds of person-to-person transmission of NiV. All of these RNA viruses pose threats to global public health due to the absence of approved vaccines or therapeutics. There is a clear unmet need for countermeasures to address the threat of natural outbreaks, epidemics, or deliberate release. The Paramyxoviridae and Bunyavirales Vaccines and Antibodies Center (PABVAX) is a well-integrated consortium conducting a set of discovery and translational research programs composed of a Data Management Core, three Scientific Cores, and five Research Projects (RPs). The synergistic activities of PABVAX partners will be focused on developing novel vaccines, treatments, and tools to foster pandemic preparedness. Federal law requires that the arenaviruses, nairoviruses, and henipaviruses used in the PABVAX Center be handled in an approved Biosafety Level (BSL)-4 containment laboratory. Core E provides an approved BSL-4 facility and a trained and highly experienced team of BSL-4 investigators and staff to perform studies that support RP1, RP2, RP4, RP5, Core C, and Core D. Core E will perform well-documented animal efficacy studies based on a quality system approach that will be supported by Core A with all data generated managed by Core B. The services provided by Core E will include 1) a secure repository of well characterized seed stocks of BSL-4 arenaviruses, nairoviruses, and henipaviruses 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 strains or variants of henipaviruses, arenaviruses, and nairoviruses to fill gaps as needed; 6) generation of tools including immune reagents and inactivated samples from animals for distribution to RPs, Cores, and other ReVAMPP Centers; 7) virus challenge, vaccination, treatment, and collection of samples from animals; 8) technical expertise and equipment to conduct clinical pathological, immunological, and virological analysis of samples and to perform necropsies in BSL...