Why I
Joined GGCP

Raised on a farm in Tennessee, I have spent my life fascinated by the creatures inhabiting our world and the things that parasitize, plague, and otherwise make life for those creatures miserable. After receiving a master’s degree in public health, I attempted to tackle some of these health problems head on as a Peace Corps volunteer working in Kazakhstan on health promotion programs to reduce the impact of zoonoses and hospital acquired infections. During this time I saw how a group of dedicated scientists could improve people’s quality of life directly. Following this experience, I knew that I wanted to make a real contribution to the world’s health as a research scientist working to reduce the burden of significant human and animal pathogens.

My dissertation is being completed in the laboratory of Dr. N. James MacLachlan in collaboration with Dr. Stuart T. Nichol at the Centers for Disease Control and Prevention, Special Pathogens Branch in Atlanta, Georgia. My work and interests focus primarily on the determinants of Rift Valley fever (RVF) and Ebola virus virulence and host pathogenesis, basic RVF virus molecular biology, the phylogenetics and evolution of the Bunyaviridae, RVF vaccine design, and development of molecular-based virus detection assays.

Rift Valley fever (RVF) virus has caused widespread epizootics/epidemics of severe animal and human disease throughout Africa and, more recently, on the Arabian peninsula. Transmitted primarily by mosquitoes, RVF virus can cause economically disastrous “abortion storms” and disease in livestock. Human infection is characterized by a self-limiting febrile illness that can, in 1-2% of individuals, progress to more serious complications, including acute hepatitis, delayed onset encephalitis, retinitis, and a hemorrhagic syndrome with high case fatality. Due to their large and explosive nature, RVF virus outbreaks can greatly strain the ability of veterinary and public health infrastructure to provide adequate medical care to affected individuals.

To gain a more complete understanding of RVF virus genomic diversity, we have recently published work (Bird et al., Journal of Virology, 2007) involving the complete genome sequence of 33 wild-type isolates collected over a period of 56 years (1944–2000) and spanning the entire known geographic range. This work revealed that the ecology of RVF virus is complex and has involved widespread movements of virus throughout Africa multiple times over its evolutionary history. Interestingly, the virus was found to have a relatively recent common ancestry dating to approximately the 1850s to 1880s. These findings suggest that dramatic ecological changes under way in Africa during the initiation of large-scale colonial agriculture in the early 1800s, accompanied by importation of large numbers of highly susceptible European breeds of livestock, may have promoted the emergence and spread of RVF virus throughout the continent.

At a more basic level, using reverse genetics, we have successfully generated recombinant RVF viruses with precisely defined genotypes that allow for identification of virus virulence factors that are important in disease pathogenesis. While in vitro studies demonstrated that the nonstructural M segment gene (NSm) of RVF virus was dispensable for virus replication and growth in cell culture (Gerrard et al., Virology, 2007), additional in vivo studies in a highly susceptible rodent animal model found that recombinant RVF virus lacking the NSm gene was attenuated (Bird et al., Virology, 2007). Previous studies of the nonstructural S segment gene (NSs) and our own recent work have revealed that both RVF virus nonstructural genes (NSm and NSs) are critical determinants of virulence with major contributions to in vivo pathogenesis and evasion of the host immune response.

The increased understanding of the molecular determinants of RVF virus virulence afforded by these studies led to development of rationally designed recombinant live-attenuated vaccine candidates for RVF virus. Utilizing reverse genetics, candidate vaccines were generated that contained complete deletions of the entire NSm and NSs genes, individually and in combination, to potentially enhance their attenuation and in vivo safety. Recently, we successfully tested the safety, immunogenicity, and efficacy of these vaccine candidates in a highly susceptible rodent model (Bird et al., Journal of Virology, 2008). The results of this study were highly promising—all of the immunized animals developed robust anti-RVF virus immunity (total IgG antibody titers ~1:6400) that was sufficient to confer protection from morbidity and mortality following challenge with a lethal dose of wild-type RVF virus. Further safety and immunogenicity testing in relevant livestock animals is planned. If proven safe and effective, these vaccine candidates may provide effective prophylactic protection for both animals and humans in endemic regions of Africa or following the natural or intentional introduction of this significant veterinary/public health threat into previously unaffected areas.

In Kabete Kenya drawing pre-vaccination bloods on sheep for a RVF vaccine trial.