A Virus-Like Particle-Based Vaccine Candidate against the Tick-Borne Powassan Virus Induces Neutralizing Antibodies in a Mouse Model.

Velasco Cimica,Sujatha Rashid,Conor Mcmahon,Debra Adams-Fish,Timothy T Stedman,Sahar Saleem,Emily Matuczinski

doi:10.3390/pathogens10060680

Velasco Cimica, Sujatha Rashid + Show 5 more

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https://doi.org/10.3390/pathogens10060680

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Journal: Pathogens	Publication Date: May 31, 2021
Citations: 6	License type: CC BY 4.0

Affiliation: American Type Culture Collection

Abstract

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.

Highlights

Powassan virus (POWV) is a tick-borne flavivirus pathogen that was first discovered and isolated in Ontario, Canada, in 1958 [1]
The POWV Envelope Domain III (EDIII) was expressed with a C-terminal histidine tag for detection and purification by immobilized metal affinity chromatography (IMAC)
SDS-PAGE and Coomassie blue staining analysis showed over 95% purity of POWV EDIII (Figure 1, panel 1), with electrophoretic mobility in agreement with the predicted molecular weight of 12.7 kDa obtained by bioinformatics analysis [21]

Summary

Introduction

Powassan virus (POWV) is a tick-borne flavivirus pathogen that was first discovered and isolated in Ontario, Canada, in 1958 [1]. In the USA, the incidence of POWV disease reported to the Centers for Disease Control and Prevention (CDC) has increased over the last two decades from about one case per year before 2005 to an average of more than 24 domestic cases annually since 2016 [6]. The emergence of POWV cases may have resulted from the virus lineage adaptation to the more aggressive tick species Ix. scapularis from the Ix. cookei that rarely bites humans. Ix. scapularis has geographically expanded in recent decades across much of the eastern and central US [4] and is a primary vector for Lyme disease and the lineage II of POWV [8]. Coincident with an increase in POWV infections, multiple states have reported their first confirmed cases in the last 5 years [9,10]. Given the increase in POWV incidence and expansion, human urbanization of rural areas, increase in the tick population, lack of therapeutics, and the potentially morbid consequences of POWV infection, proactive development of a POWV vaccine should be a public health priority

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