Vaccine Development Against West Nile Virus

Since the late 1990s, disease outbreaks associated with the mosquito-borne West Nile virus (WNV) have become a public heath concern of global significance. Outbreaks of fever and encephalitis in Eastern Europe, the Middle East and North America have resulted in almost 25,000 cases and nearly 1,500 deaths. Since its introduction into North America almost a decade ago, the virus has not only persisted, but spread throughout the USA and regions of Canada, Mexico and countries of Central and South America. In 2006, the virus caused more than 4,000 cases and 100 deaths, with an estimated 750,000 undiagnosed infections. This continued spread of the virus and sustained incidence of WNV infection indicate that the virus will remain a serious public health problem for the foreseeable future. Justifiably, considerable effort has been spent in developing a suitable vaccine and a number of experimental vaccines have shown promise in pre-clinical and clinical trials. However, the standard issues of vaccine efficacy and safety are further complicated by the fact that the population most at risk of severe and fatal WNV infection, and hence the likely recipients of vaccination, are the elderly and immunosuppressed. In a previous article (Hall and Khromykh, 2004) we extensively reviewed the status of WNV vaccines and readers are directed to this reference for details of earlier developments in the field. In this chapter we review recent developments of safe and efficacious new-generation WNV vaccines, with specific emphasis on recombinant strategies to produce infectious, clone-derived, live, attenuated preparations and non-infectious, self-replicating vaccines.