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Open AccessArticle

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

1
School of Chemistry and Molecular Biosciences, University of Queensland, St Lucia, Queensland 4072, Australia
2
School of Veterinary Science, University of Queensland Gatton Campus, Queensland 4343, Australia
3
Australian Infectious Diseases Research Centre, University of Queensland, St Lucia, Queensland 4072, Australia
*
Authors to whom correspondence should be addressed.
Current address: Australian Animal Health Laboratory, The Commonwealth Scientific and Industrial Research Organization, Geelong VIC 3219, Australia.
Vaccines 2020, 8(2), 258; https://doi.org/10.3390/vaccines8020258
Received: 28 April 2020 / Revised: 25 May 2020 / Accepted: 27 May 2020 / Published: 29 May 2020
(This article belongs to the Special Issue Update on Flavivirus Vaccines)
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. View Full-Text
Keywords: West Nile virus; insect-specific flavivirus; chimeric flavivirus; vaccine West Nile virus; insect-specific flavivirus; chimeric flavivirus; vaccine
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Vet, L.J.; Setoh, Y.X.; Amarilla, A.A.; Habarugira, G.; Suen, W.W.; Newton, N.D.; Harrison, J.J.; Hobson-Peters, J.; Hall, R.A.; Bielefeldt-Ohmann, H. Protective Efficacy of a Chimeric Insect-Specific Flavivirus Vaccine against West Nile Virus. Vaccines 2020, 8, 258.

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