Current trends in West Nile virus vaccine development

Abstract

West Nile virus (WNV) is a mosquito-borne flavivirus that has become endemic in the United States. From 1999–2012, there have been 37088 reported cases of WNV and 1549 deaths, resulting in a 4.2% case-fatality rate. Despite development of effective WNV vaccines for horses, there is no vaccine to prevent human WNV infection. Several vaccines have been tested in preclinical studies and to date there have been eight clinical trials, with promising results in terms of safety and induction of antiviral immunity. Although mass vaccination is unlikely to be cost effective, implementation of a targeted vaccine program may be feasible if a safe and effective vaccine can be brought to market. Further evaluation of new and advanced vaccine candidates is strongly encouraged.

Keywords::

• antibody
• epidemiology
• flaviviruses
• immunity
• immunocompromised
• neurotropic
• vaccination
• West Nile virus

Acknowledgements

We thank Andrew Townsend for excellent graphical design and assistance.

Financial & competing interests disclosure

OHSU, Dr Slifka, and Dr Amanna have a financial interest in Najít Technologies, Inc., a company that is developing a new West Nile virus vaccine using a hydrogen peroxide-based inactivation approach. This potential individual and institutional conflict of interest has been reviewed and managed by OHSU. This project was funded in part with federal funds from the National Institute of Allergy and Infectious Diseases, U01 AI082196 (to MKS), R44 AI079898 (to MKS and IJA), R01 AI098723 (to MKS) and Oregon National Primate Research Center grant, 8P51 OD011092-53 (to MKS). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Based on more than a decade of surveillance in the USA, it is expected that WNV will continue to threaten vulnerable populations for the foreseeable future.

• The severity of WNV disease is associated with advanced age and often results in long-term health issues including potentially severe neurological sequelae and a higher mortality rate after recovery from acute infection. More studies are needed to determine if WNV infection is linked to chronic kidney disease.

• Several early-stage vaccine clinical trials have been completed, but none has advanced to licensure.

• Reference standards for performing WNV-specific neutralization assays, including highly characterized serum standards and reference strains of WNV, should be considered.

• Due to the sporadic nature of WNV outbreaks, concerns remain regarding the feasibility of Phase III vaccine field efficacy trials. However, this may be mitigated, at least in part, by maintaining intense surveillance efforts, performing trials in locations of high/continued WNV incidence and monitoring for vaccine efficacy over a prolonged period of time (possibly 1–3 years).

• A formal cost–benefit analysis of targeted WNV vaccination should be performed, preferably including not only direct healthcare costs but also costs associated with WNV surveillance, prevention and outbreak response.

Notes