Among viruses that cause disease in humans members of the family Filoviridae, Ebola virus (EBOV) and Marburg virus (MARV), stand out for their impressive lethality: These viruses are the most deadly human pathogens known to man with reported case fatality rates of 90% in some outbreaks in Central Africa. In addition to natural outbreaks, EBOV and MARV 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 EBOV and MARV 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 therapeutics against all medically relevant strains and species of filoviruses. RPI employs recombinant vesicular stomatitis virus (VSV)-based therapeutic vaccines, RP2 focuses on anti-filovirus small interfering RNAs (siRNA), and RP3 focuses on fully human anti-filovirus monoclonal antibodies. A unique aspect of this Center is that these three approaches represent the very small cohort of countermeasures that have shown the ability to provide complete postexposure protection of nonhuman primates against filoviruses. All three of these research projects require that countermeasures be evaluated in animals against infectious Ebola and Marburg viruses. Federal law requires that these viruses 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 RPI, RP2, and RP3. Core B will perform "well-documented" nonhuman primate efficacy studies that 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 lACUC 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 nonhuman primate studies.
The BSL-4 Evaluation Core provides BSL-4 resources and expertise for RPI, RP2, and RP3. The goal of this Core is to work closely with Research Project Leaders and staff to advance the development of countermeasures against all medically relevant members of the family Filoviridae.
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