Immunogenicity of MultiTEP-Platform-Based Recombinant Protein Vaccine, PV-1950R, Targeting Three B-Cell Antigenic Determinants of Pathological α-Synuclein.
Karen ZagorskiGor ChailyanArmine HovakimyanTatevik AntonyanSepideh Kiani ShabestariIrina PetrushinaHayk DavtyanDavid H CribbsMathew Blurton-JonesEliezer MasliahMichael G AgadjanyanAnahit GhochikyanPublished in: International journal of molecular sciences (2022)
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.
Keyphrases
- mouse model
- cell free
- single cell
- circulating tumor
- white matter
- high throughput
- cell therapy
- oxidative stress
- dna damage
- single molecule
- resting state
- cancer therapy
- high fat diet induced
- type diabetes
- mild cognitive impairment
- amino acid
- parkinson disease
- brain injury
- current status
- anti inflammatory
- nucleic acid
- blood brain barrier
- subarachnoid hemorrhage