Towards a new generation of flavivirus vaccines.

Flavivirus diseases have caused great public health concern for over three centuries, with diseases like yellow fever, dengue, Japanese encephalitis and tick-borne encephalitis causing thousands of deaths. Although yellow fever epidemics can be brought under control by the use of vaccine or mosquito-control measures, there have been many examples of its re-emergence as an epidemic disease. Similarly, the use of vaccines or arthropod-control measures have failed to prevent the spread of other flaviviruses such as Japanese encephalitis virus. There has been rapid growth in the knowledge of molecular information on flaviviruses in the last decade, and on the basis of this information several potential recombinant subunit vaccines are being developed and appear to be effective experimentally. Moreover, the assumption that humoral immunity induced by virus structural envelope glycoproteins is the only effective means of providing protection against flavivirus infection can be questioned. This review attempts to summarize recent thinking in this field and to evaluate the different systems available as potential future flavivirus vaccines in inducing protective immunity.