Our research has focused on dengue virus, a pathogen transmitted by mosquitos and endemic throughout the tropical and sub-tropical world. With the recent emergence of Zika virus in the Americas we have expanded our research to include Zika, as Zika and dengue are very closely related. Our particular interest is in viral genetics and evolution and how those factors affect viral fitness, viral pathogenicity and the human immune response to dengue and Zika virus infection.
- Determinants of long-term antibody mediated dengue and Zika immunity in humans. We follow a cohort of dengue and Zika infected humans over time to study the natural evolution of immunity to the viruses over time. We focus particularly on type specific and broad antibody mediated dengue virus neutralization and the memory B cells that give rise to these type-specific and broadly neutralizing antibodies. We are particularly interested in identifying putative thresholds and mechanisms of antibody mediated protection and how natural antibody mediated immunity correlates with and influences vaccine induced immunity.
- Protein scaffold vaccines for flaviviruses. Because the flaviviruses are antigenically very similar, vaccine strategies that work for one flavivirus are expected to work for others as well. Working with Nancy Haigwood’s group at the Oregon National Primate Research Center, we have developed a dengue virus serotype 2 vaccine that uses a bacterial protein scaffold to display dengue virus envelope protein antigens. This vaccine is both immunogenic and protective in non-human primates. We are adapting this scaffold to display envelope glycoproteins from the other three dengue virus serotypes as well as Zika virus with the intent of developing a vaccine that can protect against all four dengue serotypes as well as Zika. In the future the platform may be expanded to include Yellow Fever and West Nile viruses, also closely related to dengue and important human pathogens.
- Role of dengue virus genomic RNA secondary structure in dengue virus biology. The dengue genome is encoded on a single sense strand of RNA. The RNA is known to fold back on itself to form secondary and tertiary structures. Working with Kevin Weeks’ lab at UNC Chapel, we are using dengue virus infectious clones and sub-genomic clones to study the function of these secondary and tertiary RNA structures in vivo.