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Immunogenicity of MultiTEP-Platform-Based Recombinant Protein Vaccine, PV-1950R, Targeting Three B-Cell Antigenic Determinants of Pathological α-Synuclein
Parkinson’s disease (PD) and dementia with Lewy bodies (DLB) are characterized by the aberrant accumulation of intracytoplasmic misfolded and aggregated α-synuclein (α-Syn), resulting in neurodegeneration associated with inflammation. The propagation of α-Syn aggregates from cell to cell is implicat...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9181659/ https://www.ncbi.nlm.nih.gov/pubmed/35682759 http://dx.doi.org/10.3390/ijms23116080 |
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author | Zagorski, Karen Chailyan, Gor Hovakimyan, Armine Antonyan, Tatevik Kiani Shabestari, Sepideh Petrushina, Irina Davtyan, Hayk Cribbs, David H. Blurton-Jones, Mathew Masliah, Eliezer Agadjanyan, Michael G. Ghochikyan, Anahit |
author_facet | Zagorski, Karen Chailyan, Gor Hovakimyan, Armine Antonyan, Tatevik Kiani Shabestari, Sepideh Petrushina, Irina Davtyan, Hayk Cribbs, David H. Blurton-Jones, Mathew Masliah, Eliezer Agadjanyan, Michael G. Ghochikyan, Anahit |
author_sort | Zagorski, Karen |
collection | PubMed |
description | Parkinson’s disease (PD) and dementia with Lewy bodies (DLB) are characterized by the aberrant accumulation of intracytoplasmic misfolded and aggregated α-synuclein (α-Syn), resulting in neurodegeneration associated with inflammation. The propagation of α-Syn aggregates from cell to cell is implicated in the spreading of pathological α-Syn in the brain and disease progression. We and others demonstrated that antibodies generated after active and passive vaccinations could inhibit the propagation of pathological α-Syn in the extracellular space and prevent/inhibit disease/s in the relevant animal models. We recently tested the immunogenicity and efficacy of four DNA vaccines on the basis of the universal MultiTEP platform technology in the DLB/PD mouse model. The antibodies generated by these vaccines efficiently reduced/inhibited the accumulation of pathological α-Syn in the different brain regions and improved the motor deficit of immunized female mice. The most immunogenic and preclinically effective vaccine, PV-1950D, targeting three B-cell epitopes of pathological α-Syn simultaneously, has been selected for future IND-enabling studies. However, to ensure therapeutically potent concentrations of α-Syn antibodies in the periphery of the vaccinated elderly, we developed a recombinant protein-based MultiTEP vaccine, PV-1950R/A, and tested its immunogenicity in young and aged D-line mice. Antibody responses induced by immunizations with the PV-1950R/A vaccine and its homologous DNA counterpart, PV-1950D, in a mouse model of PD/DLB have been compared. |
format | Online Article Text |
id | pubmed-9181659 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-91816592022-06-10 Immunogenicity of MultiTEP-Platform-Based Recombinant Protein Vaccine, PV-1950R, Targeting Three B-Cell Antigenic Determinants of Pathological α-Synuclein Zagorski, Karen Chailyan, Gor Hovakimyan, Armine Antonyan, Tatevik Kiani Shabestari, Sepideh Petrushina, Irina Davtyan, Hayk Cribbs, David H. Blurton-Jones, Mathew Masliah, Eliezer Agadjanyan, Michael G. Ghochikyan, Anahit Int J Mol Sci Brief Report Parkinson’s disease (PD) and dementia with Lewy bodies (DLB) are characterized by the aberrant accumulation of intracytoplasmic misfolded and aggregated α-synuclein (α-Syn), resulting in neurodegeneration associated with inflammation. The propagation of α-Syn aggregates from cell to cell is implicated in the spreading of pathological α-Syn in the brain and disease progression. We and others demonstrated that antibodies generated after active and passive vaccinations could inhibit the propagation of pathological α-Syn in the extracellular space and prevent/inhibit disease/s in the relevant animal models. We recently tested the immunogenicity and efficacy of four DNA vaccines on the basis of the universal MultiTEP platform technology in the DLB/PD mouse model. The antibodies generated by these vaccines efficiently reduced/inhibited the accumulation of pathological α-Syn in the different brain regions and improved the motor deficit of immunized female mice. The most immunogenic and preclinically effective vaccine, PV-1950D, targeting three B-cell epitopes of pathological α-Syn simultaneously, has been selected for future IND-enabling studies. However, to ensure therapeutically potent concentrations of α-Syn antibodies in the periphery of the vaccinated elderly, we developed a recombinant protein-based MultiTEP vaccine, PV-1950R/A, and tested its immunogenicity in young and aged D-line mice. Antibody responses induced by immunizations with the PV-1950R/A vaccine and its homologous DNA counterpart, PV-1950D, in a mouse model of PD/DLB have been compared. MDPI 2022-05-29 /pmc/articles/PMC9181659/ /pubmed/35682759 http://dx.doi.org/10.3390/ijms23116080 Text en © 2022 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 | Brief Report Zagorski, Karen Chailyan, Gor Hovakimyan, Armine Antonyan, Tatevik Kiani Shabestari, Sepideh Petrushina, Irina Davtyan, Hayk Cribbs, David H. Blurton-Jones, Mathew Masliah, Eliezer Agadjanyan, Michael G. Ghochikyan, Anahit Immunogenicity of MultiTEP-Platform-Based Recombinant Protein Vaccine, PV-1950R, Targeting Three B-Cell Antigenic Determinants of Pathological α-Synuclein |
title | Immunogenicity of MultiTEP-Platform-Based Recombinant Protein Vaccine, PV-1950R, Targeting Three B-Cell Antigenic Determinants of Pathological α-Synuclein |
title_full | Immunogenicity of MultiTEP-Platform-Based Recombinant Protein Vaccine, PV-1950R, Targeting Three B-Cell Antigenic Determinants of Pathological α-Synuclein |
title_fullStr | Immunogenicity of MultiTEP-Platform-Based Recombinant Protein Vaccine, PV-1950R, Targeting Three B-Cell Antigenic Determinants of Pathological α-Synuclein |
title_full_unstemmed | Immunogenicity of MultiTEP-Platform-Based Recombinant Protein Vaccine, PV-1950R, Targeting Three B-Cell Antigenic Determinants of Pathological α-Synuclein |
title_short | Immunogenicity of MultiTEP-Platform-Based Recombinant Protein Vaccine, PV-1950R, Targeting Three B-Cell Antigenic Determinants of Pathological α-Synuclein |
title_sort | immunogenicity of multitep-platform-based recombinant protein vaccine, pv-1950r, targeting three b-cell antigenic determinants of pathological α-synuclein |
topic | Brief Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9181659/ https://www.ncbi.nlm.nih.gov/pubmed/35682759 http://dx.doi.org/10.3390/ijms23116080 |
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