Efficacy and durability of a recombinant subunit West Nile vaccine candidate in protecting hamsters from West Nile encephalitis

Abstract

The efficacy of a new recombinant subunit West Nile virus (WNV) vaccine candidate was determined in a hamster model of meningoencephalitis. Groups of hamsters were immunized subcutaneously with a WNV recombinant envelope protein (80E) with or without WNV non-structural protein 1 (NS1) mixed with adjuvant or adjuvant alone. At 2 weeks, 6 months, and 12 months after two immunizations at 4 week intervals with the respective immunogens, groups of animals were challenged via the intraperitoneal route with a virulent strain of WNV. The two recombinant antigen preparations gave similar results; hamsters in both groups had a strong antibody response following immunization, and none of the animals became ill or developed detectable viremia after challenge with WNV at 2 weeks or 6 months post booster vaccination. In contrast, , mortality among the control animals at 2 weeks post booster challenge was 73%, and at 6 months post booster, the mortality was 53% among the control animals. When challenged 12 months after the booster vaccination, a low level viremia was detected in some of the vaccinated hamsters, and one hamster became sick, but recovered. In contrast, all of the control animals that received adjuvant only developed a viremia, and the mortality rate was 77%. These results with the recombinant subunit WNV vaccine are very encouraging and warrant further animal studies to evaluate its potential use to protect humans against WNV disease.

Preparation and immunogenic properties of a recombinant West Nile subunit vaccine

“…The data presented document the production and purification of the specific antigens, and their use in vaccine formulations for the generation of both cellular and humoral immune responses in vaccinated animals. The results reported in the accompanying paper [31] document the ability of the vaccine to afford protection against lethal viral infection in a hamster model of WNV encephalitis highly relevant to human disease.…”

“…In our ongoing studies on a recombinant subunit vaccine for dengue virus, the addition of NS1 to envelope protein in the vaccine increased the production of IFN-γ from antigen-stimulated immune mouse splenocytes in vitro (Lieberman, MM et al, unpublished data). Also, partial protection of hamsters against WNV encephalitis was obtained by vaccination with a formulation containing NS1 alone as the only immunogen [31].…”

“…The protective efficacy of the vaccine in the golden hamster model of West Nile encephalitis is described in an accompanying paper [31].…”

Recent advances in human flavivirus vaccines

“…Immunising mice, hamsters and rhesus macaques with HBV-002 induced high titres of neutralising antibodies and protected animals against WNV challenges [43][44][45]. A phase I clinical study was initiated in 25 flavivirus-naïve volunteers.…”

Encephalitic Flaviviruses

“…Other potential vaccine candidates include a live attenuated Schwarz strain of measles virus expressing the secreted form of E protein from a virulent strain of West Nile virus (Despres et al, 2005), a live attenuated WNV/Dengue 4 virus chimera (Pletnev et al, 2003), RepliVax WN, a defective pseudoinfectious West Nile virus lacking a functional capsid gene (Mason et al, 2006;Widman et al, 2008;Yamshchikov et al, 2004), an attenuated West Nile prototype virus (Yamshchikov et al, 2004) and a plasmid DNA vaccine containing the infectious full-length RNA genome of Kunjin (KUN) virus (Hall et al, 2003), a subtype of West Nile virus. In addition subunit vaccines including a bacterially expressed domain III of West Nile virus E protein (Chu et al, 2007;Martina et al, 2008) and a recombinant truncated E (trE) and NS1 protein construct expressed in Drosophila S2 cells Watts et al, 2007) are under investigation. As with Japanese encephalitis virus, the prospect for a human vaccine for West Nile virus infections is promising, with the leading candidates at various stages of clinical trials as well as a number of promising candidates still at the early developmental stage.…”