Evidence map›Paper›PMID 32119976›Full record

ReviewNeurobiology of disease2020

Characterization and preclinical evaluation of the cGMP grade DNA based vaccine, AV-1959D to enter the first-in-human clinical trials.

Irina Petrushina, Armine Hovakimyan, Indira S Harahap-Carrillo, Hayk Davtyan, Tatevik Antonyan, Gor Chailyan, Konstantin Kazarian, Maxim Antonenko, Amandine Jullienne, Mary M Hamer and 8 more

Open access · goldAbstract readReview
PubMed Full text at PMC Publisher
In one paragraph

Review in Neurobiology of disease, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.

0numbers the graph read from it
0cells of the map it votes in
33citing papers in PubMed
2.5field-weighted citation impact, top 10% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

33 citing papers in PubMed, 39 citations in OpenAlex.

  1. Review
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  6. Vaccines for Alzheimer's disease: a brief scoping review.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2025
    Article
  7. Review
  8. Cerebral proteome adaptations to amyloid angiopathy are prevented by carbonic anhydrase inhibitors.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025
    Article
  9. Microglial activation states and their implications for Alzheimer's Disease.The journal of prevention of Alzheimer's disease · 2025
    Review
  10. Review
  11. Immunotherapies: A Treasure Trove of Alzheimer's Disease.Current pharmaceutical biotechnology · 2025
    Review
  12. Review
  13. Article
  14. Review
  15. Review
  16. Review
  17. Article
  18. Review
  19. Article
  20. Anti-Amyloid Immunotherapies for Alzheimer's Disease: A 2023 Clinical Update.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2023
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

18 authors at 3 institutions in 1 country.

Irina PetrushinaInstitute for Memory Impairments and Neurological Disorders, University of California, Irvine, CA, USA.
Armine HovakimyanDepartment of Molecular Immunology, Institute for Molecular Medicine, Huntington Beach, CA, USA.
Indira S Harahap-CarrilloDepartment of Basic Sciences, Loma Linda University School of Medicine, Loma Linda, CA, USA.
Hayk DavtyanInstitute for Memory Impairments and Neurological Disorders, University of California, Irvine, CA, USA; Department of Molecular Immunology, Institute for Molecular Medicine, Huntington Beach, CA, USA; Sue and Bill Gross Stem Cell Research Center, University of California, Irvine, CA, USA.
Tatevik AntonyanDepartment of Molecular Immunology, Institute for Molecular Medicine, Huntington Beach, CA, USA.
Gor ChailyanDepartment of Molecular Immunology, Institute for Molecular Medicine, Huntington Beach, CA, USA.
Konstantin KazarianDepartment of Molecular Immunology, Institute for Molecular Medicine, Huntington Beach, CA, USA.
Maxim AntonenkoDepartment of Molecular Immunology, Institute for Molecular Medicine, Huntington Beach, CA, USA.
Amandine JullienneInstitute for Memory Impairments and Neurological Disorders, University of California, Irvine, CA, USA.
Mary M HamerDepartment of Pediatrics, University of California, Irvine, CA, USA.
Andre ObenausDepartment of Pediatrics, University of California, Irvine, CA, USA; Preclinical and Translational Imaging Center, University of California, Irvine, CA, USA.
Olga KingDepartment of Molecular Immunology, Institute for Molecular Medicine, Huntington Beach, CA, USA.
Karen ZagorskiDepartment of Molecular Immunology, Institute for Molecular Medicine, Huntington Beach, CA, USA.
Mathew Blurton-JonesInstitute for Memory Impairments and Neurological Disorders, University of California, Irvine, CA, USA; Sue and Bill Gross Stem Cell Research Center, University of California, Irvine, CA, USA; Department of Neurobiology and Behavior, University of California, Irvine, CA, USA.
David H CribbsInstitute for Memory Impairments and Neurological Disorders, University of California, Irvine, CA, USA.
Harry LanderDepartment of Molecular Immunology, Institute for Molecular Medicine, Huntington Beach, CA, USA.
Anahit GhochikyanDepartment of Molecular Immunology, Institute for Molecular Medicine, Huntington Beach, CA, USA. Electronic address: aghochykyan@immed.org.
Michael G AgadjanyanDepartment of Molecular Immunology, Institute for Molecular Medicine, Huntington Beach, CA, USA. Electronic address: magadjanyan@immed.org.
Institute for Molecular Medicine · USUniversity of California, Irvine · USLoma Linda University · US

Funding

Pre-clinical study to fulfill FDA requirements for the completion of AV-1959 INDU01AG048310 · NIA · INSTITUTE FOR MOLECULAR MEDICINE · PI AGADJANYAN, MICHAEL G · 2015 to 2018
$4.5M
NIA NIH HHS U01 AG048310
6 · The paper itself

Abstract

The DNA vaccine, AV-1959D, targeting N-terminal epitope of Aβ peptide, has been proven immunogenic in mice, rabbits, and non-human primates, while its therapeutic efficacy has been shown in mouse models of Alzheimer's disease (AD). Here we report for the first time on IND-enabling biodistribution and safety/toxicology studies of cGMP-grade AV-1959D vaccine in the Tg2576 mouse model of AD. We also tested acute neuropathology safety profiles of AV-1959D in another AD disease model, Tg-SwDI mice with established vascular and parenchymal Aβ pathology in a pre-clinical translational study. Biodistribution studies two days after the injection demonstrated high copy numbers of AV-1959D plasmid after single immunization of Tg2576 mice at the injection sites but not in the tissues of distant organs. Plasmids persisted at the injection sites of some mice 60 days after vaccination. In Tg2576 mice with established amyloid pathology, we did not observe short- or long-term toxicities after multiple immunizations with three doses of AV-1959D. Assessment of the repeated dose acute safety of AV-1959D in cerebral amyloid angiopathy (CAA) prone Tg-SwDI mice did not reveal any immunotherapy-induced vasogenic edema detected by magnetic resonance imaging (MRI) or increased microhemorrhages. Multiple immunizations of Tg-SwDI mice with AV-1959D did not induce T and B cell infiltration, glial activation, vascular deposition of Aβ, or neuronal degeneration (necrosis and apoptosis) greater than that in the control group determined by immunohistochemistry of brain tissues. Taken together, the safety data from two different mouse models of AD substantiate a favorable safety profile of the cGMP grade AV-1959D vaccine supporting its progression to first-in-human clinical trials.

Indexed as

Adjuvants, ImmunologicAlzheimer DiseaseAlzheimer VaccinesAmyloid beta-PeptidesAnimalsAntibody FormationCerebral Amyloid AngiopathyClinical Trials as TopicDisease Models, AnimalHumansMiceMice, TransgenicPeptide FragmentsVaccines, DNAAdjuvants, ImmunologicAlzheimer VaccinesAmyloid beta-PeptidesPeptide FragmentsVaccines, DNAAlzheimer's disease (AD)BiodistributionDNA Aβ-vaccineImmunohistochemistry (IHC)Magnetic resonance imaging (MRI)Mouse models of ADSafety toxicology

Identifiers

PMID32119976
PMCPMC8772258
OpenAlexW3008574691

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.