Abstract
Although West Nile virus (WNV) has been a prominent mosquito-transmitted infection in North America for twenty years, no human vaccine has been licensed. With a cumulative number of 24,714 neurological disease cases and 2314 deaths in the U.S. since 1999, plus a large outbreak in Europe in 2018 involving over 2000 human cases in 15 countries, a vaccine is essential to prevent continued morbidity, mortality, and economic burden. Currently, four veterinary vaccines are licensed, and six vaccines have progressed into clinical trials in humans. All four veterinary vaccines require multiple primary doses and annual boosters, but for a human vaccine to be protective and cost effective in the most vulnerable older age population, it is ideal that the vaccine be strongly immunogenic with only a single dose and without subsequent annual boosters. Of six human vaccine candidates, the two live, attenuated vaccines were the only ones that elicited strong immunity after a single dose. As none of these candidates have yet progressed beyond phase II clinical trials, development of new candidate vaccines and improvement of vaccination strategies remains an important area of research.
Highlights
North America for twenty years, no human vaccine has been licensed
For West Nile virus (WNV) vaccine development, neutralizing antibodies are typically investigated as the primary correlate of protection in both murine and human studies, and since WNV neuropathogenesis in mice is similar to that observed in humans [60], protection from murine neurological disease is predicted to correlate with protection in humans
Regardless, ChimeriVax-WN02 is the most extensively studied WNV vaccine candidate and it may be closest to licensure of the six candidate vaccines that have been evaluated in clinical trials
Summary
West Nile virus (WNV) is a member of the flavivirus genus and is related to other medically relevant mosquito-borne flaviviruses including dengue (DENV), yellow fever (YFV), Zika (ZIKV), and Japanese encephalitis (JEV) [1]. First isolated in Africa in 1937, WNV is broadly distributed across the world [2,3] It has a transmission cycle involving birds and Culex spp. mosquitoes and is the most common mosquito-borne disease in the United States [4]. 10% of WNND cases will be fatal [6]. WNV was first detected in the U.S in 1999, the first large outbreak occurred in 2002, with 2946 WNND cases and 284 deaths [6]. WNNDof cases, but this was followed byfollowed another large outbreak in 2012 This periodic pattern of large outbreaks is typical of a virus mosquito-borne virus as WNV [7].
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