ArticleAlzheimer's research & therapy2017
Evaluation of a DNA Aβ42 vaccine in adult rhesus monkeys (Macaca mulatta): antibody kinetics and immune profile after intradermal immunization with full-length DNA Aβ42 trimer.
Article in Alzheimer's research & therapy, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 21 citations in OpenAlex.
- New insights for the development of efficient DNA vaccines.Microbial biotechnology · 2024Review
- Amyloid-β targeting immunisation in aged non-human primate (Microcebus murinus).Brain, behavior, and immunity · 2023Article
- Glial cell transcriptome analyses in 3xTg-AD mice: Effects of aging, disease progression, and anti-Aβ immunotherapy.Aging brain · 2023Article
- CSF-Derived CD4Neurology(R) neuroimmunology & neuroinflammation · 2022Article
- Comparative neuropathology in aging primates: A perspective.American journal of primatology · 2021Review
- Article
- Nucleic Acid-Based Approaches for Tumor Therapy.Cells · 2020Review
- Active immunotherapy and alternative therapeutic modalities for Alzheimer's disease.Alzheimer's & dementia (New York, N. Y.) · 2020Article
- Saponins fromMolecules (Basel, Switzerland) · 2019Review
- Active full-length DNA AβAlzheimer's research & therapy · 2018Article
- Intradermal active full-length DNA Aβ42 immunization via electroporation leads to high anti-Aβ antibody levels in wild-type mice.Journal of neuroimmunology · 2018Article
- Efficacy and Safety of the Immunization with DNA for Alzheimer's Disease in Animal Models: A Systematic Review from Literature.Journal of Alzheimer's disease reports · 2017Article
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundAggregated amyloid-β peptide 1-42 (Aβ42), derived from the cellular amyloid precursor protein, is one of the pathological hallmarks of Alzheimer's disease (AD). Although active immunization against Aβ42 peptide was successful in AD mouse models and led to removal of plaques and improved memory, a similar clinical trial in humans (Aβ42 peptide immunization with QS-21 adjuvant) was stopped in phase II, when 6% of the treated patients developed encephalitis. Currently ongoing passive immunizations with the injection of preformed monoclonal antibodies against different epitopes within the Aβ
methodsSix rhesus monkeys received two different doses of a DNA Aβ42 trimer vaccine. The humoral immune response was analyzed from blood throughout the study, and cellular immune responses were determined in peripheral blood mononuclear cells (PBMCs) after three and six immunizations.
resultsDNA Aβ42 trimer immunization led to high titer antibody responses in the nonhuman primate (NHP) model. Antibodies generated in the rhesus monkeys following DNA Aβ42 immunization detected amyloid plaques consisting of human Aβ42 peptide in the brain of the triple-transgenic AD mouse model. T-cell responses showed no interferon (IFN)-γ- and interleukin (IL)-17-producing cells from PBMCs in Enzyme-Linked ImmunoSpot assays after three immunization time points. At six immunization time points, IFN-γ- and IL-17-producing cells were found in immunized animals as well as in control animals and were thus considered nonspecific and not due to the immunization regimen. IFN-γ and IL-17 secretion in response to Aβ42 peptide restimulation became undetectable after a 3-month rest period.
conclusionsIntradermal DNA Aβ42 immunization delivered with the gene gun produces a high antibody response in NHPs and is highly likely to be effective and safe in a clinical AD prevention trial in patients.
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