Immunogenicity of MultiTEP-Platform-Based Recombinant Protein Vaccine, PV-1950R, Targeting Three B-Cell Antigenic Determinants of Pathological α-Synuclein

Abstract

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.

Are Therapies That Target α-Synuclein Effective at Halting Parkinson’s Disease Progression? A Systematic Review

“…Recent studies have also evaluated the immunogenicity of a recombinant DNA vaccine to multiple B-cell epitopes of α-syn, PV-1950R, that was able to reduce total and protein-kinase-resistant α-syn [ 67 , 68 ]. Hence, active immunotherapy may prove a useful means to limit toxic α-syn accumulation and the pathological consequences that arise from its neurotoxicity.…”

Novel Vaccine against Pathological Pyroglutamate-Modified Amyloid Beta for Prevention of Alzheimer’s Disease

“…To achieve robust and reliable immunogenicity, we applied our well-characterized universal vaccine platform MultiTEP, which is currently being evaluated in multiple preclinical IND enabling studies [ 42 , 43 , 44 , 46 , 68 ] and is in a first-in-human DNA vaccine Phase I clinical trial (NCT05642429). This vaccine platform is designed to induce strong immune responses in genetically diverse populations and potentially in immunosenescence individuals by activating pre-existing memory T helper cells with select universal foreign T helper (Th) epitopes.…”

Special Issue “Neurobiology of Protein Synuclein”

“…Evidence has shown that antibodies generated after active and passive vaccinations can inhibit the spread of pathological α-syn in the extracellular space and prevent or inhibit diseases in relevant animal models. The brief report by Zagorski and collaborators [ 58 ] published in this Special Issue developed a recombinant protein-based MultiTEP vaccine and tested its immunogenicity in young and aged D-line mice.…”