Abstract
West Nile encephalitis emerged in 1999 in the United States, then rapidly spread through the North American continent causing severe disease in human and horses. Since then, outbreaks appeared in Europe, and in 2012, the United States experienced a new severe outbreak reporting a total of 5,387 cases of West Nile virus (WNV) disease in humans, including 243 deaths. So far, no human vaccine is available to control new WNV outbreaks and to avoid worldwide spreading. In this review, we discuss the state-of-the-art of West Nile vaccine development and the potential of a novel safe and effective approach based on recombinant live attenuated measles virus (MV) vaccine. MV vaccine is a live attenuated negative-stranded RNA virus proven as one of the safest, most stable and effective human vaccines. We previously described a vector derived from the Schwarz MV vaccine strain that stably expresses antigens from emerging arboviruses, such as dengue, West Nile or chikungunya viruses, and is strongly immunogenic in animal models, even in the presence of MV pre-existing immunity. A single administration of a recombinant MV vaccine expressing the secreted form of WNV envelope glycoprotein elicited protective immunity in mice and non-human primates as early as two weeks after immunization, indicating its potential as a human vaccine.
Highlights
West Nile virus (WNV), originally identified in 1937 from a febrile woman in the West Nile district of Uganda [1], is a flavivirus belonging to the Japanese encephalitis serocomplex in the Flaviviridae family, together with St Louis encephalitis (SLE), Murray Valley encephalitis (MVE), Japanese encephalitis (JE) and Kunjin (KUN) viruses
Derived from the WNV-NY99 strain grown in Vero cells, induced complete protection in mice lethally challenged with the WNV NY99 strain [80]. Another formaldehyde-inactivated vaccine based on the Israel 98 (ISR98) WNV strain propagated on retina-derived PER.C6 cells (a cell line derived from human embryonic retinal cells transformed with the Adenovirus Type 5 (Ad5) E1A and E1B genes ) was shown to be protective in geese, with protection levels correlating with neutralizing antibody titers
Other live attenuated vaccines based on mutations of glycosylation sites on the E and NS1 proteins [93] or on selected mutations in the E protein known for attenuating other flaviviruses, such as the Japanese encephalitis virus (JEV) SA-14142 strain and the ChimeriVaxWN02 vaccines, combined to mutations in the 3’-non-coding stem-loop structure, have been proposed [94]
Summary
West Nile virus (WNV), originally identified in 1937 from a febrile woman in the West Nile district of Uganda [1], is a flavivirus belonging to the Japanese encephalitis serocomplex in the Flaviviridae family, together with St Louis encephalitis (SLE), Murray Valley encephalitis (MVE), Japanese encephalitis (JE) and Kunjin (KUN) viruses. With some case, fatalities were caused by encephalitis reported in Israel in the 1950s. During the last 15 years, increasing numbers of WNV outbreaks have been associated with the appearance of more neuroinvasive strains and higher human fatalities. In 2012, the US experienced the second worst WNV outbreak, with a total of 5,387 cases of WNV disease reported, with a higher proportion of neuroinvasive cases, including 243 deaths, one third of all cases being reported in Texas [5]. Strains of lineage 1, responsible for fatal neuroinvasive disease in humans and animals, include the NY-99 strain introduced in North America [11] and the closely-related Israel 1998 strain [12]. Africa and Madagascar, has recently been introduced in Greece, Hungary and Italy and is associated with severe neuroinvasive infections in birds, horses and humans [13,14]. The main reason for that is that pharmaceutical companies claim that the market is limited for a human vaccine, and the seasonal and unpredictable nature of the infection makes the set-up of clinical trials difficult
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