ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2013
MER5101, a novel Aβ1-15:DT conjugate vaccine, generates a robust anti-Aβ antibody response and attenuates Aβ pathology and cognitive deficits in APPswe/PS1ΔE9 transgenic mice.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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27 citing papers in PubMed, 52 citations in OpenAlex.
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- Tau Pathology Profile Across a Parietal-Hippocampal Brain Network Is Associated With Spatial Reorientation Learning and Memory Performance in the 3xTg-AD Mouse.Frontiers in aging · 2021Article
- Effects of Phenylethanoid Glycosides Extracted fromBioMed research international · 2021Article
- Impaired Hippocampal-Cortical Interactions during Sleep in a Mouse Model of Alzheimer's Disease.Current biology : CB · 2020Article
- Immunotherapies for Aging-Related Neurodegenerative Diseases-Emerging Perspectives and New Targets.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2020Review
- Effector function of anti-pyroglutamate-3 Aβ antibodies affects cognitive benefit, glial activation and amyloid clearance in Alzheimer's-like mice.Alzheimer's research & therapy · 2020Article
- Impaired Spatial Reorientation in the 3xTg-AD Mouse Model of Alzheimer's Disease.Scientific reports · 2019Article
- Efficient Expression of an Alzheimer's Disease Vaccine Candidate in the Microalga Schizochytrium sp. Using the Algevir System.Molecular biotechnology · 2018Article
- A vaccine with Aβ oligomer-specific mimotope attenuates cognitive deficits and brain pathologies in transgenic mice with Alzheimer's disease.Alzheimer's research & therapy · 2017Article
- Prophylactic immunotherapy of Alzheimer's disease using recombinant amyloid-β B-cell epitope chimeric protein as subunit vaccine.Human vaccines & immunotherapeutics · 2016Article
- Alzheimer's disease Advax(CpG)- adjuvanted MultiTEP-based dual and single vaccines induce high-titer antibodies against various forms of tau and Aβ pathological molecules.Scientific reports · 2016Article
- A novel recombinant 6Aβ15-THc-C chimeric vaccine (rCV02) mitigates Alzheimer's disease-like pathology, cognitive decline and synaptic loss in aged 3 × Tg-AD mice.Scientific reports · 2016Article
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- Current Research Therapeutic Strategies for Alzheimer's Disease Treatment.Neural plasticity · 2016Review
- An anti-pyroglutamate-3 Aβ vaccine reduces plaques and improves cognition in APPswe/PS1ΔE9 mice.Neurobiology of aging · 2015Article
- Protective effects of components of the Chinese herb grassleaf sweetflag rhizome on PC12 cells incubated with amyloid-beta42.Neural regeneration research · 2015Article
- The frequency of naive and early-activated hapten-specific B cell subsets dictates the efficacy of a therapeutic vaccine against prescription opioid abuse.Journal of immunology (Baltimore, Md. : 1950) · 2015Article
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- MAS-1 adjuvant immunotherapy generates robust Th2 type and regulatory immune responses providing long-term protection from diabetes in late-stage pre-diabetic NOD mice.Autoimmunity · 2014Article
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Active amyloid-β (Aβ) immunotherapy is under investigation to prevent or treat early Alzheimer's disease (AD). In 2002, a Phase II clinical trial (AN1792) was halted due to meningoencephalitis in ∼6% of the AD patients, possibly caused by a T-cell-mediated immunological response. Thus, generating a vaccine that safely generates high anti-Aβ antibody levels in the elderly is required. In this study, MER5101, a novel conjugate of Aβ1-15 peptide (a B-cell epitope fragment) conjugated to an immunogenic carrier protein, diphtheria toxoid (DT), and formulated in a nanoparticular emulsion-based adjuvant, was administered to 10-month-old APPswe/PS1ΔE9 transgenic (Tg) and wild-type (Wt) mice. High anti-Aβ antibody levels were observed in both vaccinated APPswe/PS1ΔE9 Tg and Wt mice. Antibody isotypes were mainly IgG1 and IgG2b, suggesting a Th2-biased response. Restimulation of splenocytes with the Aβ1-15:DT conjugate resulted in a strong proliferative response, whereas proliferation was absent after restimulation with Aβ1-15 or Aβ1-40/42 peptides, indicating a cellular immune response against DT while avoiding an Aβ-specific T-cell response. Moreover, significant reductions in cerebral Aβ plaque burden, accompanied by attenuated microglial activation and increased synaptic density, were observed in MER5101-vaccinated APPswe/PS1ΔE9 Tg mice compared with Tg adjuvant controls. Last, MER5101-immunized APPswe/PS1ΔE9 Tg mice showed improvement of cognitive deficits in both contextual fear conditioning and the Morris water maze. Our novel, highly immunogenic Aβ conjugate vaccine, MER5101, shows promise for improving Aβ vaccine safety and efficacy and therefore, may be useful for preventing and/or treating early AD.
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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.