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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
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.
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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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