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

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.

Balanced T and B cell responses are required for immune protection against Powassan virus in virus-like particle vaccination

“…Interestingly, the POWV 351–359 region containing a CD8 + T cell epitope also contains an POWV-specific B cell epitope identified by Choi et al (2020) in their synthetic enhanced DNA-based POWV vaccination approach ( Choi et al, 2020 ). These concomitant findings, as well as other studies ( Cimica et al, 2021 ), underscore the benefit of a VLP-based vaccination strategy that elicits responses to B and T cell epitopes. This finding also highlights the need to better understand immune responses elicited by different vaccine formulations (i.e., different adjuvants driving T-helper profiles, T H 1 versus T H 2) to provide optimal immunity against POWV-LB.…”

A Powassan virus domain III nanoparticle immunogen elicits neutralizing and protective antibodies in mice

“…Both a lipid nanoparticle (LNP)-encapsulated modified mRNA vaccine and a synthetic DNA vaccine encoding the POWV prM and E genes elicited potently neutralizing antibodies in serum and conferred protection in lethal challenge models in mice [ 29 , 30 ]. Another study demonstrated that a POWV virus-like particle (VLP), which also included the POWV prM and E genes, elicited strong neutralizing antibody responses [ 31 ]. Our immunogen, based solely on the recombinant EDIII-subunit, elicited potently neutralizing and protective antibodies in mice.…”

“…Recent work toward POWV vaccine development, which includes the investigation of mRNA [ 29 ], DNA [ 30 ] and VLP [ 31 ] platforms, has focused on the presentation of POWV prM and E proteins as the antigen. While these platforms have demonstrated the induction of neutralizing and protective antibody responses in mice, the full prM and E proteins contain many antigenic sites, only a subset of which are targets of functional antibodies that limit POWV infection.…”

T Cells in Tick-Borne Flavivirus Encephalitis: A Review of Current Paradigms in Protection and Disease Pathology

“…These are summarized in Table 3. In general, nucleic acid-based (mRNA: [70] DNA: [70]), virus-like particle-based [77,172], and nanoparticle-based [69] vaccination strategies have been shown to be efficacious in murine models. Monoclonal antibodies elicited by vaccination have been demonstrated to be important for protection against POWV infection [63,70,173].…”