DESCRIPTION: 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 postexposure treatments approved for human use. For these reasons EBOV and MARV have recently been included as only two of eleven human pathogens and only two of four viruses on the new US Department of Health and Human Services (HHS) Tier 1 list of Category A Select Agents. While there are no licensed countermeasures for the treatment of filovirus infections there has been significant progress over the last decade in the development of experimental preventive vaccines. Preventive vaccines may have utility for lab workers or first responders; however, in the case of a bioterrorist attack or a natural outbreak, post-exposure treatments are likely to be among the most practical and useful countermeasures. All three Research Projects (RP) that comprise the Center focus on developing broad spectrum therapeutics against all medically relevant strains and species of the family Filoviridae. RP1 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 post-exposure protection of nonhuman primates (NHPs) against filoviruses. This level of readiness is a major strength and consequential advantage of our Center. The primary objective of the Advancement of Treatments for Filovirus Infections Center is to perform pivotal studies that will facilitate the development of products used for the broad spectrum treatment of EBOV and MARV infections. The synergy and cooperation among the three RPs, the Administrative Core, and the Biosafety Level (BSL)-4 Core is built into the Center by design as all three RPs work together to combine countermeasures for enhanced efficacy. Quality system data management will be employed in both the preparation of advanced stage test articles and in the conduct of animal studies.