Author: Zagorski, Karen ; Petrushina, Irina ; Kazarian, Konstantin ; Blurton-Jones, Mathew ; Cribbs, David H ; Agadjanyan, Michael G ; Ghochikyan, Anahit ; Davis, Joy ; Davtyan, Hayk ; Chen, Wesley W

BACKGROUNDBy the time clinical symptoms of Alzheimer's disease (AD) manifest in patients there is already substantial tau pathology in the brain. Recent evidence also suggests that tau pathology can become self-propagating, further accelerating disease progression. Over the last decade several groups have tested the efficacy of protein-based anti-tau immunotherapeutics in various animal models of tauopathy. Here we report on the immunological and therapeutic potency of the first anti-tau DNA vaccine based on the MultiTEP platform, AV-1980D, in THY-Tau22 transgenic mice.METHODSStarting at 3months of age, mice were immunized intramuscularly with AV-1980D vaccine targeting a tau B cell epitope spanning aa2-18 followed by electroporation (EP). Humoral and cellular immune responses in vaccinated animals were analyzed by ELISA and ELISpot, respectively. Neuropathological changes in the brains of experimental and control mice were then analyzed by biochemical (WB and ELISA) and immunohistochemical (IHC) methods at 9months of age.RESULTSEP-mediated AV-1980D vaccinations of THY-Tau22 mice induced activation of Th cells specific to the MultiTEP vaccine platform and triggered robust humoral immunity response specific to tau. Importantly, no activation of potentially harmful autoreactive Th cell responses specific to endogenous tau species was detected. The maximum titers of anti-tau antibodies were reached after two immunizations and remained slightly lower, but steady during five subsequent monthly immunizations. Vaccinations with AV-1980D followed by EP significantly reduced total tau and pS199 and AT180 phosphorylated tau levels in the brains extracts of vaccinated mice, but produced on subtle non-significant effects on other phosphorylated tau species.CONCLUSIONSThese data demonstrate that MultiTEP-based DNA epitope vaccination targeting the N-terminus of tau is highly immunogenic and therapeutically potent in the THY-Tau22 mouse model of tauopathy and indicate that EP-mediated DNA immunization is an attractive alternative to protein-based adjuvanted vaccines for inducing high concentrations of anti-tau antibodies.

Journal of Alzheimer's Disease Reports

Efficacy and Safety of the Immunization with DNA for Alzheimer’s Disease in Animal Models: A Systematic Review from Literature

Article

Author: Demarchi, Izabel Galhardo ; Martins, Yandara Akamine ; Antoniassi, Patrícia ; Tsuchida, Cristiane Jumko

BACKGROUNDAlzheimer's disease (AD) is a neurodegenerative disease that does not have a proven cure; however, one of the most promising strategies for its treatment has been DNA vaccines.OBJECTIVEThe present review is aimed to report the new developments of the efficacy and safety of DNA vaccines for AD in animal models.METHODThe method PRISMA was used for this review. The article search was made in the electronic databases PubMed, LILACS, and Scopus using the descriptors ''Alzheimer disease" and ''Vaccine, DNA". Articles published between January 2001 and September 2017 in English, Portuguese, and Spanish were included.RESULTSUpon the consensus, the researchers identified 28 original articles. The studies showed satisfying results as for the decrease of amyloid plaques in mouse, rabbits, and monkeys brains using mostly the DNA Aβ₄₂ vaccine, AV-1955, and AdPEDI-(Aβ1-6)11, mainly with a gene gun. In addition to a reduction in tau by the first DNA vaccine (AV-1980D) targeting this protein. The use of adjuvants and boosters also had positive results as they increased the destruction of the amyloid plaques and induced an anti-inflammatory response profile without side effects.CONCLUSIONThe results of DNA vaccines targeting the amyloid-β and the tau protein with or without adjuvants and boosters were promising in reducing amyloid plaques and tau protein without side effects in animals. Although there are many vaccines being tested in animals, few reach clinical trials. Thus, as a future perspective, we suggest that clinical studies should be conducted with vaccines that have been promising in animal models (e.g., DNA Aβ₄₂ vaccine, AV-1955, and AdPEDI-(Aβ1-6)11).

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Indication	Highest Phase	Country/Location	Organization	Date
Alzheimer Disease	Phase 1	US	Capo Therapeutics, Inc.	30 Jan 2022

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