Virus-Mimicking Polymer Nanocomplexes Co-Assembling HCV E1E2 and Core Proteins with TLR 7/8 Agonist—Synthesis, Characterization, and In Vivo Activity
Hepatitis C virus (HCV) is a major public health concern, and the development of an effective HCV vaccine plays an important role in the effort to prevent new infections. Supramolecular co-assembly and co-presentation of the HCV envelope E1E2 heterodimer complex and core protein presents an attracti...
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2025-01-01
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| Series: | Journal of Functional Biomaterials |
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| author | Thomas R. Fuerst Alexander Marin Sarah Jeong Liudmila Kulakova Raman Hlushko Katrina Gorga Eric A. Toth Nevil J. Singh Alexander K. Andrianov |
| author_facet | Thomas R. Fuerst Alexander Marin Sarah Jeong Liudmila Kulakova Raman Hlushko Katrina Gorga Eric A. Toth Nevil J. Singh Alexander K. Andrianov |
| author_sort | Thomas R. Fuerst |
| collection | DOAJ |
| description | Hepatitis C virus (HCV) is a major public health concern, and the development of an effective HCV vaccine plays an important role in the effort to prevent new infections. Supramolecular co-assembly and co-presentation of the HCV envelope E1E2 heterodimer complex and core protein presents an attractive vaccine design strategy for achieving effective humoral and cellular immunity. With this objective, the two antigens were non-covalently assembled with an immunostimulant (TLR 7/8 agonist) into virus-mimicking polymer nanocomplexes (VMPNs) using a biodegradable synthetic polyphosphazene delivery vehicle. The resulting assemblies were characterized using dynamic light scattering and asymmetric flow field-flow fractionation methods and directly visualized in their vitrified state by cryogenic electron microscopy. The in vivo superiority of VMPNs over the individual components and an Alum-formulated vaccine manifests in higher neutralizing antibody titers, the promotion of a balanced IgG response, and the induction of a cellular immunity—CD4+ T cell responses to core proteins. The aqueous-based spontaneous co-assembly of antigens and immunopotentiating molecules enabled by a synthetic biodegradable carrier offers a simple and effective pathway to the development of polymer-based supramolecular nanovaccine systems. |
| format | Article |
| id | doaj-art-b96d3376713d45c0829b7beaa57909ca |
| institution | Kabale University |
| issn | 2079-4983 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | MDPI AG |
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| series | Journal of Functional Biomaterials |
| spelling | doaj-art-b96d3376713d45c0829b7beaa57909ca2025-01-24T13:36:12ZengMDPI AGJournal of Functional Biomaterials2079-49832025-01-011613410.3390/jfb16010034Virus-Mimicking Polymer Nanocomplexes Co-Assembling HCV E1E2 and Core Proteins with TLR 7/8 Agonist—Synthesis, Characterization, and In Vivo ActivityThomas R. Fuerst0Alexander Marin1Sarah Jeong2Liudmila Kulakova3Raman Hlushko4Katrina Gorga5Eric A. Toth6Nevil J. Singh7Alexander K. Andrianov8Institute for Bioscience and Biotechnology Research, University of Maryland Rockville, Rockville, MD 20850, USAInstitute for Bioscience and Biotechnology Research, University of Maryland Rockville, Rockville, MD 20850, USAInstitute for Bioscience and Biotechnology Research, University of Maryland Rockville, Rockville, MD 20850, USAInstitute for Bioscience and Biotechnology Research, University of Maryland Rockville, Rockville, MD 20850, USAInstitute for Bioscience and Biotechnology Research, University of Maryland Rockville, Rockville, MD 20850, USADepartment of Microbiology & Immunology, University of Maryland School of Medicine, Baltimore, MD 21201, USAInstitute for Bioscience and Biotechnology Research, University of Maryland Rockville, Rockville, MD 20850, USADepartment of Microbiology & Immunology, University of Maryland School of Medicine, Baltimore, MD 21201, USAInstitute for Bioscience and Biotechnology Research, University of Maryland Rockville, Rockville, MD 20850, USAHepatitis C virus (HCV) is a major public health concern, and the development of an effective HCV vaccine plays an important role in the effort to prevent new infections. Supramolecular co-assembly and co-presentation of the HCV envelope E1E2 heterodimer complex and core protein presents an attractive vaccine design strategy for achieving effective humoral and cellular immunity. With this objective, the two antigens were non-covalently assembled with an immunostimulant (TLR 7/8 agonist) into virus-mimicking polymer nanocomplexes (VMPNs) using a biodegradable synthetic polyphosphazene delivery vehicle. The resulting assemblies were characterized using dynamic light scattering and asymmetric flow field-flow fractionation methods and directly visualized in their vitrified state by cryogenic electron microscopy. The in vivo superiority of VMPNs over the individual components and an Alum-formulated vaccine manifests in higher neutralizing antibody titers, the promotion of a balanced IgG response, and the induction of a cellular immunity—CD4+ T cell responses to core proteins. The aqueous-based spontaneous co-assembly of antigens and immunopotentiating molecules enabled by a synthetic biodegradable carrier offers a simple and effective pathway to the development of polymer-based supramolecular nanovaccine systems.https://www.mdpi.com/2079-4983/16/1/34polyphosphazenespolymer nanocomplexesvaccine deliveryhepatitis C virusimmunoadjuvantssupramolecular assembly |
| spellingShingle | Thomas R. Fuerst Alexander Marin Sarah Jeong Liudmila Kulakova Raman Hlushko Katrina Gorga Eric A. Toth Nevil J. Singh Alexander K. Andrianov Virus-Mimicking Polymer Nanocomplexes Co-Assembling HCV E1E2 and Core Proteins with TLR 7/8 Agonist—Synthesis, Characterization, and In Vivo Activity Journal of Functional Biomaterials polyphosphazenes polymer nanocomplexes vaccine delivery hepatitis C virus immunoadjuvants supramolecular assembly |
| title | Virus-Mimicking Polymer Nanocomplexes Co-Assembling HCV E1E2 and Core Proteins with TLR 7/8 Agonist—Synthesis, Characterization, and In Vivo Activity |
| title_full | Virus-Mimicking Polymer Nanocomplexes Co-Assembling HCV E1E2 and Core Proteins with TLR 7/8 Agonist—Synthesis, Characterization, and In Vivo Activity |
| title_fullStr | Virus-Mimicking Polymer Nanocomplexes Co-Assembling HCV E1E2 and Core Proteins with TLR 7/8 Agonist—Synthesis, Characterization, and In Vivo Activity |
| title_full_unstemmed | Virus-Mimicking Polymer Nanocomplexes Co-Assembling HCV E1E2 and Core Proteins with TLR 7/8 Agonist—Synthesis, Characterization, and In Vivo Activity |
| title_short | Virus-Mimicking Polymer Nanocomplexes Co-Assembling HCV E1E2 and Core Proteins with TLR 7/8 Agonist—Synthesis, Characterization, and In Vivo Activity |
| title_sort | virus mimicking polymer nanocomplexes co assembling hcv e1e2 and core proteins with tlr 7 8 agonist synthesis characterization and in vivo activity |
| topic | polyphosphazenes polymer nanocomplexes vaccine delivery hepatitis C virus immunoadjuvants supramolecular assembly |
| url | https://www.mdpi.com/2079-4983/16/1/34 |
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