Cargando…

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

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 surviv...

Descripción completa

Detalles Bibliográficos
Autores principales: Cimica, Velasco, Saleem, Sahar, Matuczinski, Emily, Adams-Fish, Debra, McMahon, Conor, Rashid, Sujatha, Stedman, Timothy T.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8229747/
https://www.ncbi.nlm.nih.gov/pubmed/34072726
http://dx.doi.org/10.3390/pathogens10060680
_version_ 1783713050673545216
author Cimica, Velasco
Saleem, Sahar
Matuczinski, Emily
Adams-Fish, Debra
McMahon, Conor
Rashid, Sujatha
Stedman, Timothy T.
author_facet Cimica, Velasco
Saleem, Sahar
Matuczinski, Emily
Adams-Fish, Debra
McMahon, Conor
Rashid, Sujatha
Stedman, Timothy T.
author_sort Cimica, Velasco
collection PubMed
description 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.
format Online
Article
Text
id pubmed-8229747
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-82297472021-06-26 A Virus-Like Particle-Based Vaccine Candidate against the Tick-Borne Powassan Virus Induces Neutralizing Antibodies in a Mouse Model Cimica, Velasco Saleem, Sahar Matuczinski, Emily Adams-Fish, Debra McMahon, Conor Rashid, Sujatha Stedman, Timothy T. Pathogens Article 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. MDPI 2021-05-31 /pmc/articles/PMC8229747/ /pubmed/34072726 http://dx.doi.org/10.3390/pathogens10060680 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Cimica, Velasco
Saleem, Sahar
Matuczinski, Emily
Adams-Fish, Debra
McMahon, Conor
Rashid, Sujatha
Stedman, Timothy T.
A Virus-Like Particle-Based Vaccine Candidate against the Tick-Borne Powassan Virus Induces Neutralizing Antibodies in a Mouse Model
title A Virus-Like Particle-Based Vaccine Candidate against the Tick-Borne Powassan Virus Induces Neutralizing Antibodies in a Mouse Model
title_full A Virus-Like Particle-Based Vaccine Candidate against the Tick-Borne Powassan Virus Induces Neutralizing Antibodies in a Mouse Model
title_fullStr A Virus-Like Particle-Based Vaccine Candidate against the Tick-Borne Powassan Virus Induces Neutralizing Antibodies in a Mouse Model
title_full_unstemmed A Virus-Like Particle-Based Vaccine Candidate against the Tick-Borne Powassan Virus Induces Neutralizing Antibodies in a Mouse Model
title_short A Virus-Like Particle-Based Vaccine Candidate against the Tick-Borne Powassan Virus Induces Neutralizing Antibodies in a Mouse Model
title_sort virus-like particle-based vaccine candidate against the tick-borne powassan virus induces neutralizing antibodies in a mouse model
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8229747/
https://www.ncbi.nlm.nih.gov/pubmed/34072726
http://dx.doi.org/10.3390/pathogens10060680
work_keys_str_mv AT cimicavelasco aviruslikeparticlebasedvaccinecandidateagainstthetickbornepowassanvirusinducesneutralizingantibodiesinamousemodel
AT saleemsahar aviruslikeparticlebasedvaccinecandidateagainstthetickbornepowassanvirusinducesneutralizingantibodiesinamousemodel
AT matuczinskiemily aviruslikeparticlebasedvaccinecandidateagainstthetickbornepowassanvirusinducesneutralizingantibodiesinamousemodel
AT adamsfishdebra aviruslikeparticlebasedvaccinecandidateagainstthetickbornepowassanvirusinducesneutralizingantibodiesinamousemodel
AT mcmahonconor aviruslikeparticlebasedvaccinecandidateagainstthetickbornepowassanvirusinducesneutralizingantibodiesinamousemodel
AT rashidsujatha aviruslikeparticlebasedvaccinecandidateagainstthetickbornepowassanvirusinducesneutralizingantibodiesinamousemodel
AT stedmantimothyt aviruslikeparticlebasedvaccinecandidateagainstthetickbornepowassanvirusinducesneutralizingantibodiesinamousemodel
AT cimicavelasco viruslikeparticlebasedvaccinecandidateagainstthetickbornepowassanvirusinducesneutralizingantibodiesinamousemodel
AT saleemsahar viruslikeparticlebasedvaccinecandidateagainstthetickbornepowassanvirusinducesneutralizingantibodiesinamousemodel
AT matuczinskiemily viruslikeparticlebasedvaccinecandidateagainstthetickbornepowassanvirusinducesneutralizingantibodiesinamousemodel
AT adamsfishdebra viruslikeparticlebasedvaccinecandidateagainstthetickbornepowassanvirusinducesneutralizingantibodiesinamousemodel
AT mcmahonconor viruslikeparticlebasedvaccinecandidateagainstthetickbornepowassanvirusinducesneutralizingantibodiesinamousemodel
AT rashidsujatha viruslikeparticlebasedvaccinecandidateagainstthetickbornepowassanvirusinducesneutralizingantibodiesinamousemodel
AT stedmantimothyt viruslikeparticlebasedvaccinecandidateagainstthetickbornepowassanvirusinducesneutralizingantibodiesinamousemodel