Within the past 5 years, West Nile
encephalitis has emerged as an important disease of humans and horses in Europe. In 1999, the disease appeared for the first time in the northeastern United States. West Nile virus (a mosquito-borne flavivirus) has flourished in the North American ecosystem and is expected to expand its geographic range. In this review, the rationale for a human and veterinary
vaccine is presented and a novel approach for rapid development of a molecularly-defined, live,
attenuated vaccine is described. The technology (
ChimeriVax) is applicable to the development of
vaccines against all flaviviruses, and products against
Japanese encephalitis (a close relative of West Nile) and
dengue are in or are nearing clinical trials, respectively.
ChimeriVax vaccines utilize the safe and effective
vaccine against the prototype flavivirus -
yellow fever 17D- as a live vector. Infectious clone technology is used to replace the genes encoding the pre-membrane (prM) and envelope (E)
protein of
yellow fever 17D
vaccine with the corresponding genes of the target virus (e.g., West Nile). The resulting chimeric virus contains the
antigens responsible for protection against West Nile but retains the replication efficiency of
yellow fever 17D. The
ChimeriVax technology is well-suited to the rapid development of a West Nile
vaccine, and clinical trials could begin as early as mid-2002. Other approaches to
vaccine development are briefly reviewed. The aim of this brief review is to describe the features of West Nile
encephalitis, a newly introduced
infectious disease affecting humans, horses and wildlife in the United States; the rationale for rapid development of
vaccines; and approaches to the development of
vaccines against the disease.