MultiTEP Platform-based DNA Vaccines for alpha-Synucleinopathies: Pre-clinical Evaluation of Immunogenicity and Therapeutic Potency

We have previously demonstrated that anti-Aβ DNA vaccine (AV-1959D) based on our proprietary MultiTEP platform technology is extremely immunogenic in mice, rabbits, and monkeys. Importantly, MultiTEP platform enables development of vaccines targeting pathological molecules involved in various neurod...

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Bibliographic Details
Published in:Neurobiology of aging 2017-08, Vol.59, p.156-170
Main Authors: Davtyan, Hayk, Zagorski, Karen, Petrushina, Irina, Kazarian, Konstantin, Goldberg, Natalie R.S., Petrosyan, Janet, Blurton-Jones, Mathew, Masliah, Eliezer, Cribbs, David H., Agadjanyan, Michael G., Ghochikyan, Anahit
Format: Article
Language:English
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Summary:We have previously demonstrated that anti-Aβ DNA vaccine (AV-1959D) based on our proprietary MultiTEP platform technology is extremely immunogenic in mice, rabbits, and monkeys. Importantly, MultiTEP platform enables development of vaccines targeting pathological molecules involved in various neurodegenerative disorders. Taking advantage of the universality of MultiTEP platform, we developed DNA vaccines targeting three B cell epitopes (aa85–99, aa109–126, aa126–140) of human alpha-Synuclein (hα-Syn) separately, or all three epitopes simultaneously. All four DNA vaccines (i) generate high titers of anti-hα-Syn antibodies; (ii) induce robust MultiTEP-specific Th cell responses without activation of potentially detrimental autoreactive anti-hα-Syn Th cells. Generated antibodies recognize misfolded hα-Syn produced by neuroblastoma cells, hα-Syn in the brain tissues of transgenic mouse strains and in the brain tissues of Dementia with Lewy Bodies (DLB) cases. Based on these results, the most promising vaccine targeting three B cell epitopes of hα-Syn simultaneously (PV-1950D) has been chosen for ongoing pre-clinical assessment in mouse models of hα-Syn with the aim to translate it to the human clinical trials.
ISSN:0197-4580
1558-1497
DOI:10.1016/j.neurobiolaging.2017.08.006