Abstract
West Nile virus (WNV) continues to circulate in the USA and forms a threat to the rest of the Western hemisphere. Since methods for the treatment of WNV infections are not available, there is a need for the development of safe and effective vaccines. Here, we describe the construction of a recombinant influenza virus expressing domain III of the WNV glycoprotein E (Flu-NA-DIII) and its evaluation as a WNV vaccine candidate in a mouse model. FLU-NA-DIII-vaccinated mice were protected from severe body weight loss and mortality caused by WNV infection, whereas control mice succumbed to the infection. In addition, it was shown that one subcutaneous immunization with 105 TCID50 Flu-NA-DIII provided 100% protection against challenge. Adoptive transfer experiments demonstrated that protection was mediated by antibodies and CD4+T cells. Furthermore, mice vaccinated with FLU-NA-DIII developed protective influenza virus-specific antibody titers. It was concluded that this vector system might be an attractive platform for the development of bivalent WNV-influenza vaccines.
Highlights
West Nile Virus (WNV) belongs to the genus Flavivirus and is maintained in an enzootic cycle involving birds and mosquitoes, with humans and horses as ‘‘dead-end’’ hosts
Vaccine Characterization As shown in figure 1A, with the influenza virus M1 primer set a signal of 1.1 kb was observed with the RNA extracted from both FLU-NA-DIII and FLU-NA-green fluorescent protein (GFP) virus stocks, while only the DIII primer set resulted in an amplicon of 451 bp with FLU-NA-DIII
The fact that no infectious virus could be recovered from Madin-Darby canine kidney (MDCK) cells infected with Flu-NA-DIII in presence of trypsin up to three days after infection, indicated that no wildtype influenza virus was present in the recombinant viral stock
Summary
West Nile Virus (WNV) belongs to the genus Flavivirus and is maintained in an enzootic cycle involving birds and mosquitoes, with humans and horses as ‘‘dead-end’’ hosts. Several vaccine candidates have been tested in animal models [11,12,13,14,15,16,17,18,19,20] Most of these vaccine candidates are based on the glycoprotein E (gE), which is a target for the induction of virus-neutralizing antibody responses. Subunit vaccines based on DIII have been evaluated and proven effective in preventing severe infection in mouse models [11,12]. People that are at risk for severe WNV disease are at risk for complications associated with influenza virus infections. For the prevention of influenza and its complications, annual vaccination of high risk groups including patients with chronic disease, immune-compromised subjects and the elderly is recommended. The availability of vaccines that could protect both against WNV and influenza virus infection would be desirable
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