Discrete Cross-Reactive Epitopes for Flavivirus Serological Diagnostics and Vaccines

CDC researchers have identified and characterized discrete flavivirus cross-reactive epitopes useful for improving serodiagnosis and vaccination of flaviviruses, such as dengue virus, yellow fever virus, Japanese encephalitis virus, West Nile virus and the tick-borne encephalitis viruses.

The flavivirus envelope glycoprotein is one of the primary antigens inducing protective immunity in a host. Human flavivirus infections stimulate virus species-specific as well as flavivirus-genus cross-reactive immune responses. These cross-reactive antibodies create a serious problem for serodiagnosis, especially for secondary flavivirus infections, due to the difficulty of differentiating primary from secondary cross-reactive serum antibodies. Additionally, the presence of subneutralizing levels of flavivirus cross-reactive serum antibodies in an individual may result in a dramatic increase in the severity of secondary flavivirus infections via antibody-dependent enhancement (ADE), as commonly seen with multi-serotype dengue virus infection.

To that end, the identification and characterization of amino acids incorporated into these flavivirus cross-reactive epitopes extends practical understanding of structure-function relationships important for flavivirus immunopathology. This CDC antigen-epitope technology provides important tools and insights for improving flavivirus serodiagnosis, researching the pathogenesis of ADE, and advancing the development of safe and effective flavivirus vaccines.