Preclinical Studies of Bunyaviruses

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Arthropod-borne members of the family Bunyaviridae are recognized as major causes of disease throughout the World. Epizootic outbreaks of Rift Valley fever virus (RVFV) in regions of Africa have resulted in severe disease in humans and domestic animals. Although initially confined to Africa, RVFV has spread to the Middle East and constitutes a risk to other regions. There are currently no licensed vaccines for preventing Rift Valley fever in people, although there are 2 inactivated vaccines with limited use in animals. Vaccine development: In our efforts to create live-attenuated viral vaccine candidates for the bunyavirus group, we previously generated a recombinant La Crosse virus expressing the attachment glycoproteins of Jamestown Canyon virus. The JCV/LACV chimeric virus contains full-length S and L segments derived from LACV and a chimeric M segment in which the ORF of LACV is replaced with that derived from JCV and is flanked by the non-coding regions of LACV. The results of this research were published in 2012. Although we do not currently have plans to further evaluate vaccine candidates for the California encephalitis viruses, the use of the LACV genetic background to deliver M segment protective antigens from pathogenic bunyaviruses, such as RVFV, could be an efficient method for the rapid development of live attenuated vaccines for use in humans and animals. An important benefit of the LACV-RVFV chimeric approach would be the ability to serologically distinguish RVFV-vaccinated animals from naturally-infected animals since vaccinated animals would also have detectable antibodies to LACV proteins. We have created several chimeric cDNA clones of the LACV M segment expressing the glycoprotein of RVFV. This chimeric segment is currently being used with the LACV S and L segments to generate recombinant virus. We are currently troubleshooting the inability of our rescue system to package viable virus.