West Nile Virus Vaccination Protects against Usutu Virus Disease in Mice

West Nile virus (WNV) and Usutu virus (USUV) are mosquito-borne flaviviruses that can cause neuroinvasive disease in humans. WNV and USUV circulate in both Africa and Europe and are closely related. Due to antigenic similarity, WNV-specific antibodies and USUV-specific antibodies have the potential to bind heterologous viruses; however, it is unclear whether this interaction may offer protection against infection. To investigate how prior WNV exposure would influence USUV infection, we used an attenuated WNV vaccine that contains the surface proteins of WNV in the backbone of a dengue virus 2 vaccine strain and protects against WNV disease. We hypothesized that vaccination with this attenuated WNV vaccine would protect against USUV infection. Neutralizing responses against WNV and USUV were measured in vitro using sera following vaccination. Sera from vaccinated CD-1 and Ifnar1−/− mice cross-neutralized with WNV and USUV. All mice were then subsequently challenged with an African or European USUV strain. In CD-1 mice, there was no difference in USUV titers between vaccinated and mock-vaccinated mice. However, in the Ifnar1−/− model, vaccinated mice had significantly higher survival rates and significantly lower USUV viremia compared to mock-vaccinated mice. Our results indicate that exposure to an attenuated form of WNV protects against severe USUV disease in mice and elicits a neutralizing response to both WNV and USUV. Future studies will investigate the immune mechanisms responsible for the protection against USUV infection induced by WNV vaccination, providing critical insight that will be essential for USUV and WNV vaccine development.

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Development of chimaeric West Nile virus attenuated vaccine candidate based on the Japanese encephalitis vaccine strain SA14-14-2

Journal of General Virology ◽

10.1099/vir.0.059436-0 ◽

2013 ◽

Vol 94 (12) ◽

pp. 2700-2709 ◽

Cited By ~ 12

Author(s):

Xiao-Feng Li ◽

Wei Zhao ◽

Fang Lin ◽

Qing Ye ◽

Hong-Jiang Wang ◽

...

Keyword(s):

West Nile Virus ◽

Japanese Encephalitis ◽

Vaccine Development ◽

Vaccine Candidate ◽

Genetic System ◽

Reverse Genetic System ◽

West Nile ◽

Protective Antigens ◽

Japanese Encephalitis Vaccine

Mosquito-borne flaviviruses include a large group of important human medical pathogens. Several chimaeric flaviviruses have been constructed, and show potential for vaccine development. Although Japanese encephalitis virus (JEV) live vaccine SA14-14-2 has been widely used with ideal safety and efficacy profiles, no chimaeric flavivirus based on the JEV vaccine has been described to date. Based on the reverse genetic system of the JEV vaccine SA14-14-2, a novel live chimaeric flavivirus carrying the protective antigens of West Nile virus (WNV) was constructed and recovered in this study. The resulting chimaera (ChinWNV) replicated efficiently in both mammalian and mosquito cells and possessed genetic stability after in vitro serial passaging. ChinWNV exhibited a small-plaque phenotype, and its replication was significantly restricted in mouse peripheral blood and brain compared with parental WNV. Importantly, ChinWNV was highly attenuated with regard to both neurovirulence and neuroinvasiveness in mice. Furthermore, a single ChinWNV immunization stimulated robust WNV-specific adaptive immune responses in mice, conferring significant protection against lethal WNV infection. Our results demonstrate that chimaeric flaviviruses based on the JEV vaccine can serve as a powerful platform for vaccine development, and that ChinWNV represents a potential WNV vaccine candidate that merits further development.

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Processing of the intracellular form of the west Nile virus capsid protein by the viral NS2B-NS3 protease: an in vitro study.

Journal of Virology ◽

10.1128/jvi.68.9.5765-5771.1994 ◽

1994 ◽

Vol 68 (9) ◽

pp. 5765-5771 ◽

Cited By ~ 51

Author(s):

V F Yamshchikov ◽

R W Compans

Keyword(s):

West Nile Virus ◽

Capsid Protein ◽

In Vitro Study ◽

The West ◽

West Nile ◽

Virus Capsid ◽

Intracellular Form ◽

Ns3 Protease ◽

Virus Capsid Protein

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Animal and Human Vaccines against West Nile Virus

Pathogens ◽

10.3390/pathogens9121073 ◽

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.

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Co‐Infections: Simultaneous Detections of West Nile Virus and Usutu Virus in Birds from Germany

Transboundary and Emerging Diseases ◽

10.1111/tbed.14050 ◽

2021 ◽

Author(s):

Pauline Dianne Santos ◽

Friederike Michel ◽

Claudia Wylezich ◽

Dirk Höper ◽

Markus Keller ◽

...

Keyword(s):

West Nile Virus ◽

West Nile ◽

Usutu Virus

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Screening of Mosquitoes for West Nile Virus and Usutu Virus in Croatia, 2015–2020

Tropical Medicine and Infectious Disease ◽

10.3390/tropicalmed6020045 ◽

2021 ◽

Vol 6 (2) ◽

pp. 45

Author(s):

Ana Klobucar ◽

Vladimir Savic ◽

Marcela Curman Posavec ◽

Suncica Petrinic ◽

Urska Kuhar ◽

...

Keyword(s):

West Nile Virus ◽

Culex Pipiens ◽

Rt Pcr ◽

West Nile ◽

Usutu Virus ◽

Culex Pipiens Complex ◽

Mammalian Origin ◽

Mosquito Pool ◽

The City ◽

Generation Sequencing

In the period from 2015 to 2020, an entomological survey for the presence of West Nile virus (WNV) and Usutu virus (USUV) in mosquitoes was performed in northwestern Croatia. A total of 20,363 mosquitoes were sampled in the City of Zagreb and Međimurje county, grouped in 899 pools and tested by real-time RT-PCR for WNV and USUV RNA. All pools were negative for WNV while one pool each from 2016 (Aedes albopictus), 2017 (Culex pipiens complex), 2018 (Cx. pipiens complex), and 2019 (Cx. pipiens complex), respectively, was positive for USUV. The 2018 and 2019 positive pools shared 99.31% nucleotide homology within the USUV NS5 gene and both clustered within USUV Europe 2 lineage. The next-generation sequencing of one mosquito pool (Cx. pipiens complex) collected in 2018 in Zagreb confirmed the presence of USUV and revealed several dsDNA and ssRNA viruses of insect, bacterial and mammalian origin.

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1787. The Effects of a Systemwide Diagnostic Stewardship Change on West Nile Virus Disease Ordering Practices

Open Forum Infectious Diseases ◽

10.1093/ofid/ofz360.1650 ◽

2019 ◽

Vol 6 (Supplement_2) ◽

pp. S658-S658

Author(s):

Andrew H Karaba ◽

Paul W Blair ◽

Kevin M Martin ◽

Mustapha O Saheed ◽

Karen C Carroll ◽

...

Keyword(s):

West Nile Virus ◽

Virus Disease ◽

Case Fatality ◽

Cost Savings ◽

Primary Objective ◽

Neurological Deficits ◽

West Nile ◽

Hospital System ◽

Elisa Testing ◽

Before And After

Abstract Background Neuroinvasive West Nile Virus (WNV) often leads to prolonged neurological deficits and carries a high case fatality rate. The CSF IgM (MAC-ELISA) is preferred over the CSF nucleic acid-based test (NAAT) by the CDC due to its higher sensitivity. However, our hospital system was observed to have an over-utilization of NAAT testing compared with MAC-ELISA testing. The primary objective was to compare the number of MAC-ELISA and NAAT WNV tests ordered before and after a diagnostic stewardship intervention. The secondary objectives were to determine whether this change to lead to any cost savings and increased detection of probable cases of WNV-ND. Methods In an effort to increase the use of the MAC-ELISA and to decrease unnecessary NAAT testing, the NAAT test was removed in April 2018 from the test menu in the electronic health record of a health system comprising five hospitals in the Maryland and Washington, D.C. area. NAAT testing remained possible via a paper order form. This study was a retrospective review of WNV testing done on CSF samples from July 2016 through December 2018. The seasonal and yearly number of total tests, positive tests, and total costs were determined from the period of July, 2017 to April, 2018 and were compared with May, 2018 to January, 2019. A paired t-test was performed to evaluate for differences in total testing, total positives, and total costs during non-winter months before and after the intervention. Results A total of 12.59 MAC-ELISA tests/month (95% CI: 10.29, 14.89) increased to 41 tests/month (95% CI: 34.35, 47.65) which was significantly different (P < 0.001). In contrast, there were 46.23 NAAT tests/month (95% CI: 39.55, 52.91) which decreased to 0 NAAT tests/month after the intervention (P < 0.001). This resulted in an average decrease in WNV test spending from $7200 per month to $471 per month (P < 0.001). Preceding the intervention in test ordering, 0.23% of WNV CSF tests were positive (NAAT+MAC-ELISA) while 2.44% WNV CSF tests were positive after the intervention (P = 0.03). Conclusion Elimination of electronic WNV NAAT ordering is an effective way of decreasing inappropriate WNV NAAT testing, decreasing associated costs, and may lead to improved diagnosis of WNV-ND. Disclosures All authors: No reported disclosures.

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