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 (LACV) expressing the attachment glycoproteins of Jamestown Canyon virus (JCV). The JCV/LACV chimeric virus contains full-length S and L segments derived from LACV and a chimeric M segment in which the open reading frame of LACV is replaced with that derived from JCV and is flanked by the non-coding regions of LACV. We demonstrated that chimerization did not affect the growth of the chimeric virus in tissue culture, and the virus remains highly infectious and immunogenic in Swiss Webster mice. Although both LACV and JCV parental viruses are highly neurovirulent in 21 day-old mice, the chimeric JCV/LACV is highly attenuated and does not cause disease even after intracerebral inoculation of 1000 PFU. The chimeric virus was infectious and immunogenic in rhesus monkeys and protected against the development of viremia after JCV challenge. 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.
| Bennett, R S; Gresko, A K; Nelson, J T et al. (2012) A recombinant chimeric La Crosse virus expressing the surface glycoproteins of Jamestown Canyon virus is immunogenic and protective against challenge with either parental virus in mice or monkeys. J Virol 86:420-6 |
| Bennett, Richard S; Gresko, Anthony K; Murphy, Brian R et al. (2011) Tahyna virus genetics, infectivity, and immunogenicity in mice and monkeys. Virol J 8:135 |
| Bennett, Richard S; Nelson, Jacob T; Gresko, Anthony K et al. (2011) The full genome sequence of three strains of Jamestown Canyon virus and their pathogenesis in mice or monkeys. Virol J 8:136 |
| Bennett, Richard S; Cress, Christina M; Ward, Jerrold M et al. (2008) La Crosse virus infectivity, pathogenesis, and immunogenicity in mice and monkeys. Virol J 5:25 |
