New Approaches to Flavivirus Vaccine Development

Publisher Summary This chapter discusses new approaches to flavivirus vaccine development. Flaviviruses are small, enveloped single-positive strand RNA viruses of the newly established family, Flaviviridae. Genetically and serologically related to each other, the 68 known flaviviruses include a large number of arthropod-borne agents of human disease, the most important of which, in terms of prevalence and pathogenicity, are the mosquito-borne yellow fever, dengue, and Japanese encephalitis viruses, and the far eastern and western subtypes of tick-borne encephalitis virus. The chapter presents recent advances in the molecular biology of flaviviruses that will offer novel alternatives to further flavivirus vaccine development. The capacity of medically important flaviviruses to cause lethal encephalitis in mice has been invaluable in the early assessment of candidate vaccine preparations. However, inadequacy of this model as a reliable measure of vaccine attenuation or protective immunogenicity in humans, where the pathogenesis of flaviviral disease may be vastly different, cannot be too strongly emphasized. In the case of dengue where infection of monkeys is clinically unapparent, the absence of a suitable experimental model of human infection presents a formidable barrier to the understanding of the pathogenesis of this disease and to the development of a vaccine against it.