This involves a combination of biological studies to define the virulence of the viruses in different animal systems, antigenic studies using monoclonal antibodies to identify important epitopes on viral proteins involved in virulence and protective immunity, receptor studies to elucidate the cell receptor which enables the virus to infect cells, and molecular biological research to relate the above studies to the genetics of the viruses. The yellow fever 17D live attenuated vaccine is one of the most successful vaccines ever prepared. Accordingly, we have investigated the molecular basis of attenuation of virulence and immunogenicity of the 17D virus. This information is being used towards the design of vaccines against other flavivirus diseases, such as dengue. In particular, we are investigating the potential of genetically manipulating the 17D vaccine virus as a chimeric vaccine against yellow fever and other flavivirus diseases, in particular, dengue.
Japanese encephalitis is the most common form of epidemic viral encephalitis in the world.
We are investigating the molecular basis of neurotropic disease caused by the virus and the mechanism of how the virus causes disease, including the sequelae that occur following the acute disease. Finally, we are also interested in novel approaches to vaccine development. Currently, we are exploring the use of the live tuberculosis vaccine, Mycobacterium bovis BCG, as a multivalent vaccine expressing protective immunogens of flaviviruses. Antigenic variants of yellow fever virus with an altered neurovirulence phenotype in mice. Molecular differences between wild-type Japanese encephalitis virus strains of high and low mouse neuroinvasiveness.