Our laboratory focuses on the pathogenesis of emerging and re-emerging viruses that require Biosafety level (BSL)-4 containment and on the development of countermeasures against these viruses. Our work particularly emphasizes studies on viruses causing hemorrhagic fever (HF) including Ebola virus, Marburg virus, and Lassa virus. Efforts focus on: 1) developing, refining and characterizing animal models that accurately reproduce human viral HF infection; 2) identifying critical pathogenic processes of viral HF infections that could be exploited as targets for therapeutic interventions. Particular emphasis is placed on determining the basis of coagulopathy and shock that characterize HF viral infections; and 3) measuring the therapeutic benefits of interrupting pathogenic processes that are important in the development of HF viral infection. Currently, there are no vaccines against Ebola, Marburg, or Lassa viruses approved for use in humans. Our laboratory focuses primarily on using recombinant vesicular stomatitis virus (rVSV) as a vaccine vector for viral HF. We have shown that rVSV-based HF viral vaccines can completely protect nonhuman primates against Ebola HF, Marburg HF, and Lassa fever. Specific interest areas include modifying rVSV vectors for optimal safety and immunogenicity, identifying antigens needed to develop a multiagent vaccine that can protect against major groups of HF viruses, and determining the role of cellular and host immune responses in protection.