Protective Efficacy of a Chimeric Insect-Specific Flavivirus Vaccine against West Nile Virus

Virulent strains of West Nile virus (WNV) are highly neuro-invasive and human infection is potentially lethal. However, no vaccine is currently available for human use. Here, we report the immunogenicity and protective efficacy of a vaccine derived from a chimeric virus, which was constructed using the structural proteins (prM and E) of the Kunjin strain of WNV (WNVKUN) and the genome backbone of the insect-specific flavivirus Binjari virus (BinJV). This chimeric virus (BinJ/WNVKUN-prME) exhibits an insect-specific phenotype and does not replicate in vertebrate cells. Importantly, it authentically presents the prM-E proteins of WNVKUN, which is antigenically very similar to other WNV strains and lineages. Therefore BinJ/WNVKUN-prME represents an excellent candidate to assess as a vaccine against virulent WNV strains, including the highly pathogenic WNVNY99. When CD1 mice were immunized with purified BinJ/WNVKUN-prME, they developed robust neutralizing antibody responses after a single unadjuvanted dose of 1 to 5 μg. We further demonstrated complete protection against viremia and mortality after lethal challenge with WNVNY99, with no clinical or subclinical pathology observed in vaccinated animals. These data suggest that BinJ/WNVKUN-prME represents a safe and effective WNV vaccine candidate that warrants further investigation for use in humans or in veterinary applications.

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Epidemiologic and phylogenetic analysis of the 2018 West Nile virus (WNV) outbreak in Israel demonstrates human infection of WNV lineage I

Eurosurveillance ◽

10.2807/1560-7917.es.2019.24.1.1800662 ◽

2019 ◽

Vol 24 (1) ◽

Cited By ~ 6

Author(s):

Yaniv Lustig ◽

Ruslan Gosinov ◽

Neta Zuckerman ◽

Yael Glazer ◽

Laor Orshan ◽

...

Keyword(s):

Phylogenetic Analysis ◽

West Nile Virus ◽

Human Infection ◽

European Countries ◽

West Nile

As at 12 November 2018, an outbreak of West Nile virus (WNV) was responsible for 139 WNV infection cases in Israel. Here, we characterise the epidemiology of the outbreak and demonstrate that only WNV lineage I was circulating in mosquitoes and responsible for WNV infection in humans. This suggests that the concurrence of the outbreak in Israel with WNV outbreaks in several European countries is not due to a common, more virulent WNV genotype.

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Correction: Vaccination of Mice Using the West Nile Virus E-Protein in a DNA Prime-Protein Boost Strategy Stimulates Cell-Mediated Immunity and Protects Mice against a Lethal Challenge

PLoS ONE ◽

10.1371/journal.pone.0091631 ◽

2014 ◽

Vol 9 (2) ◽

pp. e91631

Author(s):

Keyword(s):

West Nile Virus ◽

Cell Mediated Immunity ◽

The West ◽

West Nile ◽

Lethal Challenge ◽

E Protein ◽

Protein Boost

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Immunogenicity and Protective Efficacy of a Recombinant Subunit West Nile Virus Vaccine in Rhesus Monkeys

Clinical and Vaccine Immunology ◽

10.1128/cvi.00119-09 ◽

2009 ◽

Vol 16 (9) ◽

pp. 1332-1337 ◽

Cited By ~ 54

Author(s):

Michael M. Lieberman ◽

Vivek R. Nerurkar ◽

Haiyan Luo ◽

Bruce Cropp ◽

Ricardo Carrion ◽

...

Keyword(s):

West Nile Virus ◽

Cellular Immunity ◽

Cytokine Production ◽

Protective Efficacy ◽

Expression System ◽

High Yield ◽

Separate Experiment ◽

Enzyme Linked Immunosorbent Assay ◽

Control Group ◽

West Nile

ABSTRACT The immunogenicity and protective efficacy of a recombinant subunit West Nile virus (WNV) vaccine was evaluated in rhesus macaques (Macaca mulatta). The vaccine consisted of a recombinant envelope (E) protein truncated at the C-terminal end, resulting in a polypeptide containing 80% of the N-terminal amino acids of the native WNV protein (WN-80E), mixed with an adjuvant (GPI-0100). WN-80E was produced in a Drosophila melanogaster expression system with high yield and purified by immunoaffinity chromatography using a monoclonal antibody specific for flavivirus E proteins. Groups of monkeys were vaccinated with formulations containing 1 or 25 μg of WN-80E antigen, and both humoral and cellular immunity were assessed after vaccination. The results demonstrated potent antibody responses to vaccination, as determined by both enzyme-linked immunosorbent assay and virus-neutralizing antibody assays. All vaccinated animals responded favorably, and there was little difference in response between animals immunized with 1 or 25 μg of WN-80E. Cellular immunity was determined by lymphocyte proliferation and cytokine production assays using peripheral blood mononuclear cells from vaccinated animals stimulated in vitro with WN-80E. Cell-mediated immune responses varied from animal to animal within each group. About half of the animals responded with lymphoproliferation, cytokine production, or both. Again, there was little difference in response between animals immunized with a 1- or 25-μg dose of WN-80E in the vaccine formulations. In a separate experiment, groups of monkeys were immunized with the WN-80E/GPI-0100 vaccine or an adjuvant-only control formulation. Animals were then challenged by inoculation of wild-type WNV, and the level of viremia in each animal was monitored daily for 10 days. The results showed that whereas all animals in the control group had detectable viremia for at least 3 days after challenge, all of the vaccinated animals were negative on all days after challenge. Thus, the WN-80E vaccine was 100% efficacious in protecting monkeys against infection with WNV.

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Proximity of Residence to Bodies of Water and Risk for West Nile Virus Infection: A Case-Control Study in Houston, Texas

Journal of Biomedicine and Biotechnology ◽

10.1155/2012/159578 ◽

2012 ◽

Vol 2012 ◽

pp. 1-6 ◽

Cited By ~ 5

Author(s):

Melissa S. Nolan ◽

Ana Zangeneh ◽

Salma A. Khuwaja ◽

Diana Martinez ◽

Susan N. Rossmann ◽

...

Keyword(s):

West Nile Virus ◽

Disease Surveillance ◽

West Nile Virus Infection ◽

Water Source ◽

Water Sources ◽

Human Infection ◽

West Nile ◽

Transmission Cycle ◽

Increased Risk ◽

Slow Moving

West Nile virus (WNV), a mosquito-borne virus, has clinically affected hundreds of residents in the Houston metropolitan area since its introduction in 2002. This study aimed to determine if living within close proximity to a water source increases one’s odds of infection with WNV. We identified 356 eligible WNV-positive cases and 356 controls using a population proportionate to size model with US Census Bureau data. We found that living near slow moving water sources was statistically associated with increased odds for human infection, while living near moderate moving water systems was associated with decreased odds for human infection. Living near bayous lined with vegetation as opposed to concrete also showed increased risk of infection. The habitats of slow moving and vegetation lined water sources appear to favor the mosquito-human transmission cycle. These methods can be used by resource-limited health entities to identify high-risk areas for arboviral disease surveillance and efficient mosquito management initiatives.

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Neuroinvasive West Nile Virus Disease in Canada. The Saskatchewan Experience

Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques ◽

10.1017/s0317167100014700 ◽

2013 ◽

Vol 40 (4) ◽

pp. 580-584 ◽

Cited By ~ 7

Author(s):

José F. Téllez-Zenteno ◽

Gary Hunter ◽

Lizbeth Hernández-Ronquillo ◽

Edrish Haghir

Keyword(s):

West Nile Virus ◽

Virus Disease ◽

Neurological Complications ◽

Human Infection ◽

Infected Mosquito ◽

Surveillance Program ◽

West Nile ◽

Outdoor Sports ◽

History Of ◽

The Government

Abstract:Background:West Nile virus (WNV) is a virus of the family Flaviviridae. The main route of human infection is through the bite of an infected mosquito. Approximately 90% of WNV infections in humans are asymptomatic, but neurologic manifestations can be severe.Methods:This study reviews the clinical profile of cases with neuroinvasive West Nile infection (NWNI) reported by the Surveillance program of the government of Saskatchewan in the Saskatoon Health Region (SHR). In 2007, 1456 cases of human West Nile cases were reported by the government of Saskatchewan in the whole province. One hundred and thirteen cases had severe symptoms of NWNI (8%), 1172 (80%) cases had mild symptoms of WNI and 171 (12%) had asymptomatic disease. Three hundred and fifty six cases were reported in the SHR, where 57 (16%) fulfilled criteria for NWNI.Results:From the 57 cases, 39 (68%) were females. Nine (16%) patients had a history of recent camping, two (4%) reported outdoor sports and four (8%) reported outdoor activities not otherwise specified. Twenty five patients had headache (43.9%), 25 confusion (42.1%), 23 meningitis (40.4%), 17 encephalitis (29.8%), 14 encephalopathy (24.6%), 11 meningoencephalitis (19.3%), 10 tremor (17.5%), acute flaccid paralysis 10 (17.5%), myoclonus 1 (1.8%), nystagmus 2 (3.5%), diplopia 2 (3.5%), dizziness 2 (3.5%). Three patients died related with comorbidities during admission.Conclusion:During a year of high occurrence of WNI in Saskatchewan, 16% of cases developed NWNI. The recognition of neurological complications associated with WNI is important to improve their referral to tertiary centers.

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Replication-Defective West Nile Virus with NS1 Deletion as a New Vaccine Platform for Flavivirus

Journal of Virology ◽

10.1128/jvi.00720-19 ◽

2019 ◽

Vol 93 (17) ◽

Cited By ~ 2

Author(s):

Na Li ◽

Ya-Nan Zhang ◽

Cheng-Lin Deng ◽

Pei-Yong Shi ◽

Zhi-Ming Yuan ◽

...

Keyword(s):

Single Dose ◽

West Nile Virus ◽

Cell Line ◽

Vaccine Development ◽

Vero Cells ◽

High Dose ◽

Ns1 Protein ◽

Vaccine Platform ◽

West Nile ◽

Flavivirus Vaccine

ABSTRACTWe previously produced a replication-defective West Nile virus (WNV) lacking NS1 (WNV-ΔNS1) that could propagate at low levels (105infectious units [IU]/ml) in a 293T cell line expressing wild-type (WT) NS1. This finding indicates the potential of developing WNV-ΔNS1 as a noninfectious vaccine. To explore this idea, we developed an NS1-expressing Vero cell line (VeroNS1) that significantly improved the yield of WNV-ΔNS1 (108 IU/ml). We evaluated the safety and efficacy of WNV-ΔNS1 in mice. WNV-ΔNS1 appeared to be safe, as no replicative virus was found in naive Vero cells after continuous culturing of WNV-ΔNS1 in VeroNS1cells for 15 rounds. WNV-ΔNS1 was noninfectious in mice, even when IFNAR−/−mice were administered a high dose of WNV-ΔNS1. Vaccination with a single dose of WNV-ΔNS1 protected mice from a highly lethal challenge with WT WNV. The antibody response against WNV correlated well with the protection of vaccinated mice. Our study demonstrates the potential of the NS1transcomplementation system as a new platform for flavivirus vaccine development.IMPORTANCEMany flaviviruses are significant human pathogens that frequently cause outbreaks and epidemics around the world. Development of novel vaccine platforms against these pathogens is a public health priority. Using WNV as a model, we developed a new vaccine platform for flaviviruses. WNV containing a NS1 deletion (WNV-ΔNS1) could be efficientlytranscomplemented in Vero cells that constitutively expressed WT NS1 protein. A single-dose immunization with WNV-ΔNS1 elicited robust immune responses in mice. The immunized animals were fully protected against pathogenic WNV infection. No adverse effects related to the WNV-ΔNS1 vaccination were observed. The results have demonstrated the potential of the NS1 complementation system as an alternative platform for flavivirus vaccine development, especially for highly pathogenic flaviviruses.

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Serological evidence of West Nile virus infection in the horse population of northern Serbia

The Journal of Infection in Developing Countries ◽

10.3855/jidc.3885 ◽

2014 ◽

Vol 8 (07) ◽

pp. 914-918 ◽

Cited By ~ 6

Author(s):

Strahinja Medić ◽

Rene Van den Hoven ◽

Tamaš Petrović ◽

Diana Lupulović ◽

Norbert Nowotny

Keyword(s):

West Nile Virus ◽

West Nile Virus Infection ◽

Neutralizing Antibody ◽

Manuscript Preparation ◽

Serum Samples ◽

West Nile ◽

Horse Population ◽

Antibody Titers ◽

Antibody Elisa ◽

Lineage 2

Introduction: This study was conducted to evaluate the seroprevalence of West Nile virus (WNV) in the horse population of northern Serbia. Furthermore, it aimed to provide insight and an updated overview on the circulation of this re-emerging pathogen in this part of southeastern Europe. At the time of manuscript preparation, no clinical cases of WNV infection in horses were reported in this area. Methodology: Between 2007 and 2011, a total of 252 equine serum samples were collected from seven different locations in northern Serbia. The presence of WNV-reactive IgG antibodies was examined by using commercial and in-house ELISAs. Selected ELISA-positive samples were re-tested by a WNV lineage 2 plaque reduction neutralization test 90% (PRNT-90). Results: In 28.6% of the 252 tested equine serum samples antibodies against WNV were detected. The results obtained with the in-house ELISA corresponded to the outcome of the commercial kit in 90% of the samples. All selected WNV antibody ELISA-positive samples were confirmed by PRNT-90 with neutralizing antibody titers of 1:23 to > 1:512. Conclusion: This study confirms the circulation of WNV in northern Serbia. No striking regional differences in seroprevalences were identified suggesting WNV circulation also in other parts of Serbia. Distances between wetlands or forests and stud farms do not appear to have an influence on WNV seroprevalence.

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