Skin Vaccination with Ebola Virus Glycoprotein Using a Polyphosphazene-Based Microneedle Patch Protects Mice against Lethal Challenge
Ebolavirus (EBOV) infection in humans is a severe and often fatal disease, which demands effective interventional strategies for its prevention and treatment. The available vaccines, which are authorized under exceptional circumstances, use viral vector platforms and have serious disadvantages, such...
Main Authors: | , , , , , , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
MDPI AG
2022-12-01
|
Series: | Journal of Functional Biomaterials |
Subjects: | |
Online Access: | https://www.mdpi.com/2079-4983/14/1/16 |
_version_ | 1797440488702214144 |
---|---|
author | Andrey Romanyuk Ruixue Wang Alexander Marin Benjamin M. Janus Eric I. Felner Dengning Xia Yenny Goez-Gazi Kendra J. Alfson Abdul S. Yunus Eric A. Toth Gilad Ofek Ricardo Carrion Mark R. Prausnitz Thomas R. Fuerst Alexander K. Andrianov |
author_facet | Andrey Romanyuk Ruixue Wang Alexander Marin Benjamin M. Janus Eric I. Felner Dengning Xia Yenny Goez-Gazi Kendra J. Alfson Abdul S. Yunus Eric A. Toth Gilad Ofek Ricardo Carrion Mark R. Prausnitz Thomas R. Fuerst Alexander K. Andrianov |
author_sort | Andrey Romanyuk |
collection | DOAJ |
description | Ebolavirus (EBOV) infection in humans is a severe and often fatal disease, which demands effective interventional strategies for its prevention and treatment. The available vaccines, which are authorized under exceptional circumstances, use viral vector platforms and have serious disadvantages, such as difficulties in adapting to new virus variants, reliance on cold chain supply networks, and administration by hypodermic injection. Microneedle (MN) patches, which are made of an array of micron-scale, solid needles that painlessly penetrate into the upper layers of the skin and dissolve to deliver vaccines intradermally, simplify vaccination and can thereby increase vaccine access, especially in resource-constrained or emergency settings. The present study describes a novel MN technology, which combines EBOV glycoprotein (GP) antigen with a polyphosphazene-based immunoadjuvant and vaccine delivery system (poly[di(carboxylatophenoxy)phosphazene], PCPP). The protein-stabilizing effect of PCPP in the microfabrication process enabled preparation of a dissolvable EBOV GP MN patch vaccine with superior antigenicity compared to a non-polyphosphazene polymer-based analog. Intradermal immunization of mice with polyphosphazene-based MN patches induced strong, long-lasting antibody responses against EBOV GP, which was comparable to intramuscular injection. Moreover, mice vaccinated with the MN patches were completely protected against a lethal challenge using mouse-adapted EBOV and had no histologic lesions associated with ebolavirus disease. |
first_indexed | 2024-03-09T12:08:55Z |
format | Article |
id | doaj.art-a885540978ff4542aea23a7fac2aa739 |
institution | Directory Open Access Journal |
issn | 2079-4983 |
language | English |
last_indexed | 2024-03-09T12:08:55Z |
publishDate | 2022-12-01 |
publisher | MDPI AG |
record_format | Article |
series | Journal of Functional Biomaterials |
spelling | doaj.art-a885540978ff4542aea23a7fac2aa7392023-11-30T22:54:52ZengMDPI AGJournal of Functional Biomaterials2079-49832022-12-011411610.3390/jfb14010016Skin Vaccination with Ebola Virus Glycoprotein Using a Polyphosphazene-Based Microneedle Patch Protects Mice against Lethal ChallengeAndrey Romanyuk0Ruixue Wang1Alexander Marin2Benjamin M. Janus3Eric I. Felner4Dengning Xia5Yenny Goez-Gazi6Kendra J. Alfson7Abdul S. Yunus8Eric A. Toth9Gilad Ofek10Ricardo Carrion11Mark R. Prausnitz12Thomas R. Fuerst13Alexander K. Andrianov14School of Chemical and Biomolecular Engineering, Georgia Institute of Technology, Atlanta, GA 30332, USAInstitute for Bioscience and Biotechnology Research, University of Maryland, Rockville, MD 20850, USAInstitute for Bioscience and Biotechnology Research, University of Maryland, Rockville, MD 20850, USAInstitute for Bioscience and Biotechnology Research, University of Maryland, Rockville, MD 20850, USASchool of Chemical and Biomolecular Engineering, Georgia Institute of Technology, Atlanta, GA 30332, USASchool of Chemical and Biomolecular Engineering, Georgia Institute of Technology, Atlanta, GA 30332, USATexas Biomedical Research Institute, San Antonio, TX 78227, USATexas Biomedical Research Institute, San Antonio, TX 78227, USAInstitute for Bioscience and Biotechnology Research, University of Maryland, Rockville, MD 20850, USAInstitute for Bioscience and Biotechnology Research, University of Maryland, Rockville, MD 20850, USAInstitute for Bioscience and Biotechnology Research, University of Maryland, Rockville, MD 20850, USATexas Biomedical Research Institute, San Antonio, TX 78227, USASchool of Chemical and Biomolecular Engineering, Georgia Institute of Technology, Atlanta, GA 30332, USAInstitute for Bioscience and Biotechnology Research, University of Maryland, Rockville, MD 20850, USAInstitute for Bioscience and Biotechnology Research, University of Maryland, Rockville, MD 20850, USAEbolavirus (EBOV) infection in humans is a severe and often fatal disease, which demands effective interventional strategies for its prevention and treatment. The available vaccines, which are authorized under exceptional circumstances, use viral vector platforms and have serious disadvantages, such as difficulties in adapting to new virus variants, reliance on cold chain supply networks, and administration by hypodermic injection. Microneedle (MN) patches, which are made of an array of micron-scale, solid needles that painlessly penetrate into the upper layers of the skin and dissolve to deliver vaccines intradermally, simplify vaccination and can thereby increase vaccine access, especially in resource-constrained or emergency settings. The present study describes a novel MN technology, which combines EBOV glycoprotein (GP) antigen with a polyphosphazene-based immunoadjuvant and vaccine delivery system (poly[di(carboxylatophenoxy)phosphazene], PCPP). The protein-stabilizing effect of PCPP in the microfabrication process enabled preparation of a dissolvable EBOV GP MN patch vaccine with superior antigenicity compared to a non-polyphosphazene polymer-based analog. Intradermal immunization of mice with polyphosphazene-based MN patches induced strong, long-lasting antibody responses against EBOV GP, which was comparable to intramuscular injection. Moreover, mice vaccinated with the MN patches were completely protected against a lethal challenge using mouse-adapted EBOV and had no histologic lesions associated with ebolavirus disease.https://www.mdpi.com/2079-4983/14/1/16microneedle patchpolyphosphazeneimmunoadjuvantEbola vaccineintradermal immunizationsupramolecular assembly |
spellingShingle | Andrey Romanyuk Ruixue Wang Alexander Marin Benjamin M. Janus Eric I. Felner Dengning Xia Yenny Goez-Gazi Kendra J. Alfson Abdul S. Yunus Eric A. Toth Gilad Ofek Ricardo Carrion Mark R. Prausnitz Thomas R. Fuerst Alexander K. Andrianov Skin Vaccination with Ebola Virus Glycoprotein Using a Polyphosphazene-Based Microneedle Patch Protects Mice against Lethal Challenge Journal of Functional Biomaterials microneedle patch polyphosphazene immunoadjuvant Ebola vaccine intradermal immunization supramolecular assembly |
title | Skin Vaccination with Ebola Virus Glycoprotein Using a Polyphosphazene-Based Microneedle Patch Protects Mice against Lethal Challenge |
title_full | Skin Vaccination with Ebola Virus Glycoprotein Using a Polyphosphazene-Based Microneedle Patch Protects Mice against Lethal Challenge |
title_fullStr | Skin Vaccination with Ebola Virus Glycoprotein Using a Polyphosphazene-Based Microneedle Patch Protects Mice against Lethal Challenge |
title_full_unstemmed | Skin Vaccination with Ebola Virus Glycoprotein Using a Polyphosphazene-Based Microneedle Patch Protects Mice against Lethal Challenge |
title_short | Skin Vaccination with Ebola Virus Glycoprotein Using a Polyphosphazene-Based Microneedle Patch Protects Mice against Lethal Challenge |
title_sort | skin vaccination with ebola virus glycoprotein using a polyphosphazene based microneedle patch protects mice against lethal challenge |
topic | microneedle patch polyphosphazene immunoadjuvant Ebola vaccine intradermal immunization supramolecular assembly |
url | https://www.mdpi.com/2079-4983/14/1/16 |
work_keys_str_mv | AT andreyromanyuk skinvaccinationwithebolavirusglycoproteinusingapolyphosphazenebasedmicroneedlepatchprotectsmiceagainstlethalchallenge AT ruixuewang skinvaccinationwithebolavirusglycoproteinusingapolyphosphazenebasedmicroneedlepatchprotectsmiceagainstlethalchallenge AT alexandermarin skinvaccinationwithebolavirusglycoproteinusingapolyphosphazenebasedmicroneedlepatchprotectsmiceagainstlethalchallenge AT benjaminmjanus skinvaccinationwithebolavirusglycoproteinusingapolyphosphazenebasedmicroneedlepatchprotectsmiceagainstlethalchallenge AT ericifelner skinvaccinationwithebolavirusglycoproteinusingapolyphosphazenebasedmicroneedlepatchprotectsmiceagainstlethalchallenge AT dengningxia skinvaccinationwithebolavirusglycoproteinusingapolyphosphazenebasedmicroneedlepatchprotectsmiceagainstlethalchallenge AT yennygoezgazi skinvaccinationwithebolavirusglycoproteinusingapolyphosphazenebasedmicroneedlepatchprotectsmiceagainstlethalchallenge AT kendrajalfson skinvaccinationwithebolavirusglycoproteinusingapolyphosphazenebasedmicroneedlepatchprotectsmiceagainstlethalchallenge AT abdulsyunus skinvaccinationwithebolavirusglycoproteinusingapolyphosphazenebasedmicroneedlepatchprotectsmiceagainstlethalchallenge AT ericatoth skinvaccinationwithebolavirusglycoproteinusingapolyphosphazenebasedmicroneedlepatchprotectsmiceagainstlethalchallenge AT giladofek skinvaccinationwithebolavirusglycoproteinusingapolyphosphazenebasedmicroneedlepatchprotectsmiceagainstlethalchallenge AT ricardocarrion skinvaccinationwithebolavirusglycoproteinusingapolyphosphazenebasedmicroneedlepatchprotectsmiceagainstlethalchallenge AT markrprausnitz skinvaccinationwithebolavirusglycoproteinusingapolyphosphazenebasedmicroneedlepatchprotectsmiceagainstlethalchallenge AT thomasrfuerst skinvaccinationwithebolavirusglycoproteinusingapolyphosphazenebasedmicroneedlepatchprotectsmiceagainstlethalchallenge AT alexanderkandrianov skinvaccinationwithebolavirusglycoproteinusingapolyphosphazenebasedmicroneedlepatchprotectsmiceagainstlethalchallenge |