期刊
PATHOGENS
卷 10, 期 6, 页码 -出版社
MDPI
DOI: 10.3390/pathogens10060680
关键词
Powassan virus; vaccine; virus-like particle; POWV; VLP; flavivirus
类别
资金
- ATCC Internal Research and Development funds
Powassan virus (POWV) is a tick-borne flavivirus that can cause severe neuroinvasive diseases in North America and the Russian Far East, with no approved vaccines or specific therapeutics available. A novel POW-VLP vaccine candidate was developed and shown to generate high antigenicity and neutralizing antibody levels in immunized mice. This provides a strategy for inducing protective antibodies against Powassan neuroinvasive infection.
Powassan virus (POWV) is a tick-borne flavivirus circulating in North America and the Russian Far East that can cause severe neuroinvasive diseases, including encephalitis, meningitis, and meningoencephalitis. The reported neuroinvasive case fatality is about 10%, and approximately 50% of the survivors from the neuroinfection exhibit long-lasting or permanent neurological sequelae. Currently, treatment of POWV infection is supportive, and no FDA-approved vaccines or specific therapeutics are available. A novel Powassan vaccine candidate was created using virus-like particle technology (POW-VLP) and assembled with the viral structural proteins pre-Membrane (prM) and Envelope (E). Western blot immunoassay demonstrated high antigenicity of POW-VLP structural proteins. Transmission electron microscopy indicated that the POW-VLP exhibited icosahedral morphology typical of flaviviruses. A dose-escalation study in a murine model was performed to test immunogenicity and safety. Serum antibody was tested by ELISA, demonstrating that POW-VLP afforded 100% seroconversion to the E protein. Reporter viral-particle neutralization assay demonstrated high levels of neutralizing antibodies in the serum of immunized mice. Hybridomas expressing monoclonal antibodies were produced following POW-VLP immunization. The POW-VLP vaccine candidate created in this study provides a strategy for inducing protective antibodies against Powassan neuroinvasive infection.
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