Evidence map›Paper›PMID 40145301›Full record

ArticleAlzheimer's & dementia : the journal of the Alzheimer's Association2025

Targeting of phosphorylated tau at threonine 181 by a Qβ virus-like particle vaccine is safe, highly immunogenic, and reduces disease severity in mice and rhesus macaques.

Nicole M Maphis, Jonathan Hulse, Julianne Peabody, Somayeh Dadras, Madelin J Whelpley, Manas Kandath, Colin Wilson, Sasha Hobson, Jeff Thompson, Suttinee Poolsup and 11 more

Abstract read
In one paragraph

Article in Alzheimer's & dementia : the journal of the Alzheimer's Association, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
–field-weighted citation impact
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

5 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Article
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

21 authors.

Nicole M MaphisDepartment of Neuroscience, 1 University of New Mexico, Albuquerque, New Mexico, USA.
Jonathan HulseDepartment of Molecular Genetics and Microbiology, 1 University of New Mexico, Albuquerque, New Mexico, USA.
Julianne PeabodyDepartment of Molecular Genetics and Microbiology, 1 University of New Mexico, Albuquerque, New Mexico, USA.
Somayeh DadrasDepartment of Molecular Genetics and Microbiology, 1 University of New Mexico, Albuquerque, New Mexico, USA.
Madelin J WhelpleyDepartment of Molecular Genetics and Microbiology, 1 University of New Mexico, Albuquerque, New Mexico, USA.
Manas KandathDepartment of Molecular Genetics and Microbiology, 1 University of New Mexico, Albuquerque, New Mexico, USA.
Colin WilsonDepartment of Radiology, 1 University of New Mexico, Albuquerque, New Mexico, USA.
Sasha HobsonCenter for Memory and Aging, 1 University of New Mexico, Albuquerque, New Mexico, USA.
Jeff ThompsonCenter for Memory and Aging, 1 University of New Mexico, Albuquerque, New Mexico, USA.
Suttinee PoolsupDepartment of Molecular Genetics and Microbiology, 1 University of New Mexico, Albuquerque, New Mexico, USA.
Danielle BeckmanCalifornia National Primate Research Center, University of California, Davis, California, USA.
Sean P OttCalifornia National Primate Research Center, University of California, Davis, California, USA.
Jennifer W WatanabeCalifornia National Primate Research Center, University of California, Davis, California, USA.
Jodie L UsachenkoCalifornia National Primate Research Center, University of California, Davis, California, USA.
Koen K Van RompayCalifornia National Primate Research Center, University of California, Davis, California, USA.
John MorrisonCalifornia National Primate Research Center, University of California, Davis, California, USA.
Reed SelwynDepartment of Radiology, 1 University of New Mexico, Albuquerque, New Mexico, USA.
Gary RosenbergCenter for Memory and Aging, 1 University of New Mexico, Albuquerque, New Mexico, USA.
Janice KnoefelCenter for Memory and Aging, 1 University of New Mexico, Albuquerque, New Mexico, USA.
Bryce ChackerianDepartment of Molecular Genetics and Microbiology, 1 University of New Mexico, Albuquerque, New Mexico, USA.
Kiran BhaskarDepartment of Molecular Genetics and Microbiology, 1 University of New Mexico, Albuquerque, New Mexico, USA.

Funding

National Institute on Aging (NIA) ColonyP51OD011107 · OD · UNIVERSITY OF CALIFORNIA AT DAVIS · PI Simon J. Atkinson · 2012 to 2026
$191.5M
National Centralized Repository for Alzheimer's Disease and Related Dementias (NCRAD)U24AG021886 · NIA · INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS · PI TATIANA M. FOROUD · 2002 to 2026
$119.8M
Unfolded Protein Response and Autophagy in T Helper Cell Effector FunctionP20GM121176 · NIGMS · UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR · PI Samuel Joseph Endicott · 2017 to 2026
$24.9M
University of New Mexico (UNM) Center for Brain Recovery and RepairP20GM109089 · NIGMS · UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR · PI SHUTTLEWORTH, CLAUDE W · 2015 to 2024
$22.7M
Research Education ComponentP30AG086404 · NIA · UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR · PI John Chalmers Adair · 2024 to 2026
$17.7M
FAIR Data Competency and Machine Learning Readiness for Biomedical ScientistsK12GM088021 · NIGMS · UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR · PI REBECCA S. HARTLEY, Diane Lidke · 2009 to 2026
$16.4M
Biology of Infectious Diseases &InflammationT32AI007538 · NIAID · UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR · PI Michelle A Ozbun · 1998 to 2026
$5.2M
Scientific CoreP20AG068077 · NIA · UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR · PI ROSENBERG, GARY ALLEN · 2020 to 2022
$3.1M
The Role of Inflammasome Signaling in TauopathiesRF1NS083704 · NINDS · UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR · PI BHASKAR, KIRAN · 2020 to 2020
$2.7M
The role of inflammasome signaling in tauopathiesR01NS083704 · NINDS · UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR · PI BHASKAR, KIRAN · 2014 to 2018
$1.4M
Autophagy, Inflammation, and Metabolism (AIM) CoBRE Center P20GM121176-04Center for Brain Recovery and Repair Pre-Clinical Core P20GM109089CNPRC Pilot Program P51OD011107Institutional Research and Academic Career Development Award IRACDA # NIH K12GM088021National Centralized Repository for Alzheimer's Disease and Related Dementias (NCRAD) U24AG21886National Institute on Aging - MarkVCID-II U24AG21886National Institutes of Health to the California National Primate Research CenterNew Mexico Alzheimer's Disease Research Center (NM ADRC) P30AG086404-01New Mexico Higher Education Department - Technology Enhancement Fund (TEF)NIAID NIH HHS T32 AI007538NIA NIH HHS P20 AG068077NIA NIH HHS P30 AG086404NIA NIH HHS U24 AG021886NIGMS NIH HHS IRACDANIGMS NIH HHS K12 GM088021NIGMS NIH HHS K12GM088021NIGMS NIH HHS P20 GM109089NIGMS NIH HHS P20 GM121176NIH HHS P51 OD011107NIH Office of the Director P51OD011107NIH Research Evaluation and Commercialization Hubs (REACH) Loan Repayment ProgramNINDS NIH HHS R01 NS083704NINDS NIH HHS R01NS083704NINDS NIH HHS RF1 NS083704NINDS NIH HHS RF1NS083704-05A1University of New Mexico (UNM) Health Sciences Center Bridge SupportUNM Center for Biomedical Research Excellence (CoBRE)UNM Department of Molecular Genetics and Microbiology intradepartmental grant
6 · The paper itself

Abstract

introductionPathological accumulation of tau (pTau) contributes to various tauopathies, including Alzheimer's disease (AD), and correlates with cognitive decline. A rapid surge in tau-targeted approaches via anti-sense oligonucleotides, active/passive immunotherapies suggests that targeting p-Tau is a viable strategy against tauopathies.

methodWe describe a multi-species validation of our previously described Qß virus-like particle (VLP)-based vaccine technology targeting phosphorylated tau on threonine 181 (pT181-Qß).

resultsTwo vaccine doses of pT181-Qß, without any adjuvants, elicited robust antibody responses in two different mouse models of tauopathy (PS19 and hTau) and rhesus macaques. In mouse models, vaccination reduced AT180+ hyperphosphorylated, Sarkosyl insoluble, Gallyas silver positive tau, inflammasomes/neuroinflammation, and improved recognition memory and motor function without inducing adverse T-cell activation. Anti-pT181 antibodies are reactive to pTau in human AD brains, engage pT181+ tau in human brain lysates, and are central nervous system bioavailable. DISCUSSION: Our results suggest the translational utility of pT181-Qß against tauopathies. HIGHLIGHTS: Icosahedral display of phosphorylated tau at threonine 181 (pT181) Qß virus-like particle surface ("pT181-Qß" vaccine) induces a robust immune response in mice and in non-human primates (NHPs) pT181-Qß vaccination reduces pathological tau (pTau) and brain atrophy, and improves memory and motor function in PS19 and hTau mice. pT181-Qß vaccination-induced immunoglobulin Gs (IgGs) are safe, Th2 skewed (anti-inflammatory), specific to pTau in human AD brain, and efficiently engage pT181 in NHPs and human brain lysate. pT181

Indexed as

Alzheimer DiseaseTauopathiestau ProteinsVaccines, Virus-Like ParticleAnimalsBrainDisease Models, AnimalFemaleHumansMacaca mulattaMaleMicePhosphorylationThreoninetau ProteinsThreonineVaccines, Virus-Like ParticleAlzheimer's diseasehTauimmunotherapymild cognitive impairmentnon‐human primatesPS19pT181rhesus macaquestautauopathiesvaccinesvirus‐like particles

Identifiers

PMID40145301
PMCPMC11947757

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Registered trials

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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.