Flaviviruses and their antigenic structure.

Flaviviruses comprise important arthropod-transmitted human pathogens, including yellow fever (YF), dengue (Den), Japanese encephalitis (JE), West Nile (WN) and tick-borne encephalitis (TBE) viruses that have the potential of expanding their endemic areas due to global climatic, ecological and socio-economic changes. While effective vaccines against YF, JE and TBE are in widespread use, the development of a dengue vaccine has been hampered for a long time because of concerns of immunopathological consequences of vaccination. Phase III clinical trials with a recombinant chimeric live vaccine are now ongoing and will show whether the enormous problem of dengue can be resolved or at least reduced by vaccination in the future. Unprecedented details of the flavivirus particle structure have become available through the combined use of X-ray crystallography and cryo-electron microscopy that led to novel and surprising insights into the antigenic structure of these viruses. Recent studies provided evidence for an important role of virus maturation as well as particle dynamics in virus neutralization by antibodies and thus added previously unknown layers of complexity to our understanding of flavivirus immune protection. This information is invaluable for interpreting current investigations on the functional activities of polyclonal antibody responses to flavivirus infections and vaccinations and may open new avenues for studies on flavivirus cell biology and vaccine design.