? BSL-4 Evaluation Core (Core B) Among viruses that cause disease in humans the filoviruses, Ebolavirus and Marburgvirus, stand out for their impressive lethality. These viruses are the most deadly human pathogens known to man with reported case fatality rates of up to 90%. The recent unprecedented 2013-16 epidemic of Zaire ebolavirus in West Africa resulting in over 28,000 cases and 11,000 deaths demonstrates the ability of filoviruses to emerge in new regions. In addition to natural outbreaks, Ebolavirus and Marburgvirus are known to have been the subjects of former biological weapons programs and have the potential for deliberate misuse. Currently, there are no filovirus vaccines or treatments approved for human use. For these reasons Ebolavirus and Marburgvirus have recently been included as only two of eleven human pathogens on the new US Department of Health and Human Services (HHS) Tier 1 list of Category A select agents. All three of the Research Projects within the Center focus on developing broad spectrum rapid acting vaccines or therapeutics against all medically relevant variants and species of filoviruses. RP1 employs recombinant vesicular stomatitis virus (VSV)-based rapid acting vaccines, RP2 focuses on fully human anti-filovirus monoclonal antibodies, and RP3 focuses on anti-filovirus small interfering RNAs, small molecule antivirals, and combination treatments. A unique aspect of this Center is that these approaches represent a very small cohort of medical countermeasures that have shown the ability to provide complete single injection vaccination or therapeutic protection of nonhuman primates (NHPs) against filoviruses. All three Center Research Projects require that countermeasures be evaluated in animals against infectious filoviruses. Federal law requires that filoviruses be handled in an approved Biosafety Level (BSL)-4 containment laboratory. Core B 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-RP3. Core B will perform ?well-documented? NHP efficacy studies and also ?pivotal? NHP studies that will be conducted in accordance with a GLP-based quality agreement and will be supported by a dedicated quality assurance/quality control team. The services provided by Core B will include 1) a secure repository of well characterized seed stocks of BSL-4 filoviruses; 2) in vitro antiviral activity assays; 3) procurement of UTMB IACUC approval of animal protocols; 3) procurement, housing, and husbandry of animals; 5) virus challenge, treatment, and collection of samples from animals; 6) technical expertise and equipment to conduct clinical pathological and virological analysis of samples and to perform necropsies in BLS-4 containment; 7) histopathological analysis of tissues collected from animals infected with filoviruses; and 8) quality systems management of all records and data collected from NHP studies.