Evidence map›Paper›PMID 31847886›Full record

ArticleAlzheimer's research & therapy2019

Testing a MultiTEP-based combination vaccine to reduce Aβ and tau pathology in Tau22/5xFAD bigenic mice.

Hayk Davtyan, Armine Hovakimyan, Sepideh Kiani Shabestari, Tatevik Antonyan, Morgan A Coburn, Karen Zagorski, Gor Chailyan, Irina Petrushina, Olga Svystun, Emma Danhash and 5 more

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

Article in Alzheimer's research & therapy, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
2.2field-weighted citation impact, top 12% 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

25 citing papers in PubMed, 35 citations in OpenAlex.

  1. Review
  2. Review
  3. Article
  4. Review
  5. Article
  6. Microglial activation states and their implications for Alzheimer's Disease.The journal of prevention of Alzheimer's disease · 2025
    Review
  7. Review
  8. Review
  9. Article
  10. Article
  11. Review
  12. Review
  13. Article
  14. Article
  15. Article
  16. Article
  17. Review
  18. Article
  19. Review
  20. 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

15 authors at 4 institutions in 2 countries.

Hayk DavtyanDepartment of Molecular Immunology, Institute for Molecular Medicine, Huntington Beach, CA, USA. hdavtyan@uci.edu.ORCID 0000-0001-8554-6456
Armine HovakimyanDepartment of Molecular Immunology, Institute for Molecular Medicine, Huntington Beach, CA, USA.
Sepideh Kiani ShabestariSue and Bill Gross Stem Cell Research Center, University of California, Irvine, Irvine, CA, USA.
Tatevik AntonyanDepartment of Molecular Immunology, Institute for Molecular Medicine, Huntington Beach, CA, USA.
Morgan A CoburnSue and Bill Gross Stem Cell Research Center, University of California, Irvine, Irvine, CA, USA.
Karen ZagorskiDepartment of Molecular Immunology, Institute for Molecular Medicine, Huntington Beach, CA, USA.
Gor ChailyanDepartment of Molecular Immunology, Institute for Molecular Medicine, Huntington Beach, CA, USA.
Irina PetrushinaInstitute for Memory Impairments and Neurological Disorders, University of California, Irvine, Irvine, CA, USA.
Olga SvystunDepartment of Molecular Immunology, Institute for Molecular Medicine, Huntington Beach, CA, USA.
Emma DanhashInstitute for Memory Impairments and Neurological Disorders, University of California, Irvine, Irvine, CA, USA.
Nikolai PetrovskyFlinders University and Vaxine Pty Ltd, Adelaide, Australia.
David H CribbsInstitute for Memory Impairments and Neurological Disorders, University of California, Irvine, Irvine, CA, USA.
Michael G AgadjanyanDepartment of Molecular Immunology, Institute for Molecular Medicine, Huntington Beach, CA, USA.
Mathew Blurton-JonesInstitute for Memory Impairments and Neurological Disorders, University of California, Irvine, Irvine, CA, USA.
Anahit GhochikyanDepartment of Molecular Immunology, Institute for Molecular Medicine, Huntington Beach, CA, USA.
University of California, Irvine · USInstitute for Molecular Medicine · USFlinders University · AUNebraska Medical Center · US

Funding

UC Irvine Alzheimer's Disease Research Center Induced Pluripotent Stem Cell CoreP50AG016573 · NIA · UNIVERSITY OF CALIFORNIA-IRVINE · PI LAFERLA, FRANK M · 2000 to 2019
$37.0M
TISSUE REPOSITORY COREP01AG000538 · NIA · UNIVERSITY OF CALIFORNIA-IRVINE · PI LAFERLA, FRANK M · 1985 to 2018
$24.8M
Repurposing of Universal and Immunogenic MultiTEP Platform Designed for AD to Develop SARS-CoV-2 Multiepitope VaccineU01AG060965 · NIA · INSTITUTE FOR MOLECULAR MEDICINE · PI AGADJANYAN, MICHAEL G · 2019 to 2023
$11.0M
Combining AD Epitope Vaccine with Innate ImmunityR01NS050895 · NINDS · UNIVERSITY OF CALIFORNIA-IRVINE · PI AGADJANYAN, MICHAEL G, CRIBBS, DAVID HASTINGS · 2004 to 2018
$7.4M
Multiple Approaches to Abeta Vaccination in Animal ModelsR01AG020241 · NIA · UNIVERSITY OF CALIFORNIA-IRVINE · PI AGADJANYAN, MICHAEL G, CRIBBS, DAVID HASTINGS · 2001 to 2016
$5.6M
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
Novel vaccine adjuvants to counter bioterrorist threatsU01AI061142 · NIAID · FLINDERS UNIVERSITY OF SOUTH AUSTRALIA · PI PETROVSKY, NIKOLAI · 2005 to 2009
$3.5M
Multiple Approaches to Abeta Vaccination in Animal ModelsRF1AG020241 · NIA · INSTITUTE FOR MOLECULAR MEDICINE · PI AGADJANYAN, MICHAEL G, CRIBBS, DAVID HASTINGS · 2018 to 2018
$3.3M
Using human iPSC derived microglia and chimeric models to examine the role of PLCG2 in Alzheimers diseaseR01AG061895 · NIA · UNIVERSITY OF CALIFORNIA-IRVINE · PI DAVTYAN, HAYK · 2018 to 2022
$2.9M
Examining the role of adaptive immunity in Alzheimer's Disease pathogenesisRF1AG055524 · NIA · UNIVERSITY OF CALIFORNIA-IRVINE · PI BLURTON-JONES, MATHEW MARK · 2017 to 2017
$2.7M
Immunogenicity & efficacy of chimeric flu virus expressing Ab42 B cell epitopeR01NS057395 · NINDS · INSTITUTE FOR MOLECULAR MEDICINE · PI AGADJANYAN, MICHAEL G · 2008 to 2012
$2.0M
Manipulating DNA repair enzymes to examine the interactions between aging and Alzheimers disease with iPSC-derived microgliaR01AG056303 · NIA · UNIVERSITY OF CALIFORNIA-IRVINE · PI BLURTON-JONES, MATHEW MARK · 2017 to 2021
$1.9M
NIAID NIH HHS HHSN272200800039CNIAID NIH HHS R01 AI044809NIAID NIH HHS U01 AI061142NIA NIH HHS P01 AG000538NIA NIH HHS P50 AG016573NIA NIH HHS R01 AG020241NIA NIH HHS R01 AG056303NIA NIH HHS R01 AG061895NIA NIH HHS RF1 AG020241NIA NIH HHS RF1 AG048099NIA NIH HHS RF1 AG055524NIA NIH HHS U01 AG048310NIA NIH HHS U01 AG060965NIH HHS HHS-N272200800039CNIH HHS HHS-N272201400053CNIH HHS R01-AG055524NINDS NIH HHS R01 NS050895NINDS NIH HHS R01 NS057395NINDS NIH HHS R21 NS101504
6 · The paper itself

Abstract

backgroundAlzheimer disease (AD) is characterized by the accumulation of beta-amyloid (Aβ) plaques and neurofibrillary tangles composed of hyperphosphorylated tau, which together lead to neurodegeneration and cognitive decline. Current therapeutic approaches have primarily aimed to reduce pathological aggregates of either Aβ or tau, yet phase 3 clinical trials of these approaches have thus far failed to delay disease progression in humans. Strong preclinical evidence indicates that these two abnormally aggregated proteins interact synergistically to drive downstream neurodegeneration. Therefore, combinatorial therapies that concurrently target both Aβ and tau might be needed for effective disease modification.

methodsA combinatorial vaccination approach was designed to concurrently target both Aβ and tau pathologies. Tau22/5xFAD (T5x) bigenic mice that develop both pathological Aβ and tau aggregates were injected intramuscularly with a mixture of two MultiTEP epitope vaccines: AV-1959R and AV-1980R, targeting Aβ and tau, respectively, and formulated in Advax

resultsT5x mice immunized with a mixture of Aβ- and tau-targeting vaccines generated high Aβ- and tau-specific antibody titers that recognized senile plaques and neurofibrillary tangles/neuropil threads in human AD brain sections. Production of these antibodies in turn led to significant reductions in the levels of soluble and insoluble total tau, and hyperphosphorylated tau as well as insoluble Aβ

conclusionsAV-1959R and AV-1980R formulated with Advax

Indexed as

Alzheimer VaccinesAlzheimer DiseaseAmyloid beta-PeptidesAnimalsBrainDisease Models, AnimalMiceMice, TransgenicNeurofibrillary Tanglestau ProteinsAlzheimer VaccinesAmyloid beta-Peptidestau ProteinsAdjuvantAlzheimer’s diseaseAntibodyAβ42 and tau pathologyBigenic miceMultiTEP platformProtein epitope vaccineT5x mice

Identifiers

PMID31847886
PMCPMC6918571
OpenAlexW2996673863

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.