scholarly journals Twenty Years of Progress Toward West Nile Virus Vaccine Development

Viruses ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 823 ◽  
Author(s):  
Jaclyn A. Kaiser ◽  
Alan D.T. Barrett
Keyword(s):  
Clinical Trials ◽  
Single Dose ◽  
West Nile Virus ◽  
Vaccine Development ◽  
Cost Effective ◽  
Cumulative Number ◽  
West Nile ◽  
Transmitted Infection ◽  
Large Outbreak ◽  
Human Vaccine

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.

scholarly journals Animal and Human Vaccines against West Nile Virus

Pathogens ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 1073
Author(s):  
Juan-Carlos Saiz
Keyword(s):  
Clinical Trials ◽  
West Nile Virus ◽  
Vaccine Development ◽  
Phase Iii ◽  
West Nile ◽  
Specific Therapy ◽  
Phase Iii Clinical Trials ◽  
Neuroinvasive Disease ◽  
The Us ◽  
The Status

West Nile virus (WNV) is a widely distributed enveloped flavivirus transmitted by mosquitoes, which main hosts are birds. The virus sporadically infects equids and humans with serious economic and health consequences, as infected individuals can develop a severe neuroinvasive disease that can even lead to death. Nowadays, no WNV-specific therapy is available and vaccines are only licensed for use in horses but not for humans. While several methodologies for WNV vaccine development have been successfully applied and have contributed to significantly reducing its incidence in horses in the US, none have progressed to phase III clinical trials in humans. This review addresses the status of WNV vaccines for horses, birds, and humans, summarizing and discussing the challenges they face for their clinical advance and their introduction to the market.

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

2019 ◽  
Vol 93 (17) ◽  
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.

scholarly journals Human West Nile Virus Lineage 2 Infection: Epidemiological, Clinical, and Virological Findings

Viruses ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 458 ◽  
Author(s):  
Monia Pacenti ◽  
Alessandro Sinigaglia ◽  
Elisa Franchin ◽  
Silvana Pagni ◽  
Enrico Lavezzo ◽  
...  
Keyword(s):  
West Nile Virus ◽  
Blood Donors ◽  
Case Fatality ◽  
West Nile ◽  
Neuroinvasive Disease ◽  
Human West Nile Virus ◽  
Large Outbreak ◽  
Study Population ◽  
Lineage 2

West Nile virus (WNV) lineage 2 is expanding and causing large outbreaks in Europe. In this study, we analyzed the epidemiological, clinical, and virological features of WNV lineage 2 infection during the large outbreak that occurred in northern Italy in 2018. The study population included 86 patients with neuroinvasive disease (WNND), 307 with fever (WNF), and 34 blood donors. Phylogenetic analysis of WNV full genome sequences from patients’ samples showed that the virus belonged to the widespread central/southern European clade of WNV lineage 2 and was circulating in the area at least since 2014. The incidence of WNND and WNF progressively increased with age and was higher in males than in females. Among WNND patients, the case fatality rate was 22%. About 70% of blood donors reported symptoms during follow-up. Within the first week after symptom onset, WNV RNA was detectable in the blood or urine of 80% of patients, while 20% and 40% of WNND and WNF patients, respectively, were WNV IgM-seronegative. In CSF samples of WNND patients, WNV RNA was typically detectable when WNV IgM antibodies were absent. Blunted or no WNV IgM response and high WNV IgG levels were observed in seven patients with previous flavivirus immunity.

scholarly journals Protection of a Single Dose West Nile Virus Recombinant Subviral Particle Vaccine against Lineage 1 or 2 Strains and Analysis of the Cross-Reactivity with Usutu Virus

PLoS ONE ◽  
2014 ◽  
Vol 9 (9) ◽  
pp. e108056 ◽  
Author(s):  
Teresa Merino-Ramos ◽  
Ana-Belén Blázquez ◽  
Estela Escribano-Romero ◽  
Rodrigo Cañas-Arranz ◽  
Francisco Sobrino ◽  
...  
Keyword(s):  
Single Dose ◽  
West Nile Virus ◽  
Cross Reactivity ◽  
West Nile ◽  
Usutu Virus ◽  
Virus Recombinant ◽  
The Cross ◽  
Subviral Particle

scholarly journals Novel infectious diseases in europe

2017 ◽  
Vol 70 (11-12) ◽  
pp. 385-390
Author(s):  
Dajana Lendak ◽  
Tomislav Preveden ◽  
Nadica Kovacevic ◽  
Slavica Tomic ◽  
Maja Ruzic ◽  
...  
Keyword(s):  
West Nile Virus ◽  
Infectious Diseases ◽  
Zika Virus ◽  
Ebola Virus ◽  
Cost Effective ◽  
Hepatitis E ◽  
West Nile ◽  
Human Contact ◽  
Fast Spreading ◽  
Virus Zika

Introduction. The end of 20th and beginning of 21st century is marked by the discovery of new, supercontagious and fast spreading viral diseases. Since 1967, more than 40 new agents have been identified, including human immunodeficiency virus, Ebola, Marburg fever, severe acute respiratory syndrome, hepatitis C, hepatitis E viruses and Zika virus. Modern lifestyle, availability and speed of air traffic, migrations, as well as climate changes, enable faster spreading of infectious diseases from the regions that were hardly reachable. We selected a few diseases that raised the greatest attention among experts and public in general. Ebola. Ebola virus raises anxiety due to high mortality and fast spreading by using inter-human contact. Zika virus. Zika virus, that most often causes mild symptoms, is potentially responsible for microcephaly in neonates. Dengue. Dengue virus is an ?old story?, but in last decades incidence has multiplied by 30. West Nile virus. Although discovered in 1937, West Nile virus has been found exclusively in rural parts of Africa, while nowadays it represents one of the most important etiological factors of viral meningo-encephalitis all over the world. Hepatitis E. Today it is well-known that hepatitis E virus can cause not only acute viral hepatitis but also potentially blood-transmitted chronic hepatitis in immunocompromised, as well as some neurological disorders. Conclusion. One of the scientific challenges in the future will certainly be the discovery of available and cost-effective diagnostic tests, as well as efficient and safe vaccines for these diseases. Up to now, efficient prophylaxis is available only for Denga virus.

West Nile Virus: Veterinary Health and Vaccine Development

2019 ◽  
Vol 56 (6) ◽  
pp. 1463-1466
Author(s):  
Angela M Bosco-Lauth ◽  
Richard A Bowen
Keyword(s):  
West Nile Virus ◽  
Vaccine Development ◽  
Rapid Development ◽  
West Nile ◽  
Pet Owners ◽  
Naturally Occurring ◽  
Dead End ◽  
Avian Pathogen ◽  
Clinical Consequences ◽  
Equine Industry

Abstract West Nile virus (WNV) (Flaviviridae: Flavivirus) was discovered in Africa more than 80 yr ago and became recognized as an avian pathogen and a cause of neurologic disease in horses largely during periodic incursions into Europe. Introduction of WNV into North America stimulated great anxiety, particularly in the equine industry, but also for pet owners and livestock producers concerned about the effect of WNV on other domestic animals. Numerous subsequent studies of naturally occurring and experimentally induced disease greatly expanded our understanding of the host range and clinical consequences of WNV infection in diverse species and led to rapid development and deployment of efficacious vaccines for horses. In addition to humans, horses are clearly the animals most frequently affected by serious, sometimes lethal disease following infection with WNV, but are dead-end hosts due to the low-magnitude viremia they develop. Dogs, cats, and livestock species including chickens are readily infected with WNV, but only occasionally develop clinical disease and are considered dead-end hosts for the virus.

Vaccine Development Against West Nile Virus

2009 ◽  
pp. 427-451
Author(s):  
Alexander A. Khromykh ◽  
David C. Chang ◽  
Roy A. Hall
Keyword(s):  
West Nile Virus ◽  
Vaccine Development ◽  
West Nile

scholarly journals Current trends in West Nile virus vaccine development

2014 ◽  
Vol 13 (5) ◽  
pp. 589-608 ◽  
Author(s):  
Ian J Amanna ◽  
Mark K Slifka
Keyword(s):  
West Nile Virus ◽  
Virus Vaccine ◽  
Vaccine Development ◽  
West Nile ◽  
Current Trends
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