Hemorrhagic fever is an illness caused by viruses representing several distinct families of viruses, many of which have no cure. Filoviruses, such as Ebola Virus and Marburg virus, are examples of agents that induce hemorrhagic fever and for which mortality can be 90 percent. The increased frequency of outbreaks of hemorrhagic fever caused by Ebola and Marburg in central and western Africa and the potential use of such agents as biological weapons underscore the need to understand pathogenesis of these viruses and to develop effective intervention strategies. These viruses have also been responsible for an 88 percent decline in the world’s chimpanzee populations since 2003. Carrion’s research program uses SFBR’s biosafety level 4 (BSL-4) laboratory to safely study these agents and advance the development of vaccines and therapies for hemorrhagic fever.
In support of filovirus vaccine development, Carrion and his colleagues have developed the common marmoset as a nonhuman primate model for Ebola and Marburg hemorrhagic fever. Marmosets are small new world monkeys weighing less than 400 grams. A single intramuscular injection of 10 PFU of either virus was sufficient to induce hemorrhagic fever resembling human infection. Animals experienced weight loss, fever, high virus titers in tissue, thrombocytopenia, neutrophelia, high liver transaminases as phosphatases and disseminated intravascular coagulation. The other striking finding in these animals was lymphoid necrosis and lymphocytic depletion observed in spleen. These findings provide support for the use of the common marmoset as a small nonhuman primate model for filovirus induced hemorrhagic fever. Identification of a small nonhuman primate model for filovirus disease of the size of rodents is important as they are more predictive of therapeutic efficacy than traditional small animal models.
The second focus of Carrion’s research is development of candidate vaccines for hemorrhagic fever. Most recently Carrion and his colleagues have been awarded contracts to test the efficacy several vaccine platforms against filoviruses. Vaccines being tested by Carrion’s team include multivalent virus like particle (VLP) vaccines, adeno-vectored vaccines and modified vaccinia ankara (MVA) vaccines. Most have shown efficacy in smaller animal models and will be validated in nonhuman primate models of disease at Texas Biomed.
The third focus of Carrion’s research is development of new detection methods for bioterror agents. Most recently Carrion has teamed with a local biotechnology company to test a Handheld Aptamer-Magnetic Bead-Quantum Dot Sensor for Crimean Congo Hemorrhagic Fever (CCHF). CCHF is a tickborne disease causing hemorrhagic fever in eastern Europe, Asia, India and Africa. Overall fatality in patients hospitalized for the disease ranges from 9 percent to 50 percent.