ArticleThe Journal of clinical investigation2018
Exposure to wild-type AAV drives distinct capsid immunity profiles in humans.
Article in The Journal of clinical investigation, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers.
What it found
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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.
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.
Who cites it
67 citing papers in PubMed, 99 citations in OpenAlex.
- Trial
- Re-administration of AAV-mediated gene therapy for OTOF-related deafness: a single-arm trial.Nature medicine · 2026Article
- Comparative Transcriptomic Profiling Reveals Differences in Initiation of Antiviral Response in Low rAAV Producing HEK293 Suspension Cells.Biotechnology journal · 2026Article
- Transient prophylactic immunosuppression with abatacept or dasatinib prevents immune responses in AAV gene transfer.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Immunogenicity of Gene and Cell Therapies.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2026Review
- Current regulatory requirements for assessment of immunogenicity for gene therapy medicinal products.Cell reports. Medicine · 2025Review
- 3D co-cultures of primary human hepatocytes and Kupffer-like cells to address innate immune responses to rAAV.Scientific reports · 2025Article
- Innate immune response to AAV-based gene therapy vectors: Mechanisms of complement activation and cytokine release.Molecular therapy. Methods & clinical development · 2025Article
- Can Sex-based Variations in the Immune Responses to AAV Gene Therapy Affect Safety and Efficacy? A Review of Current Understanding.The AAPS journal · 2025Review
- Extracellular Vesicles Administered via Intrathecal Injection Mediate Safe Delivery of Nucleic Acids to the Central Nervous System for Gene Therapy.Journal of extracellular vesicles · 2025Article
- AAV vectors trigger DNA damage response-dependent pro-inflammatory signalling in human iPSC-derived CNS models and mouse brain.Nature communications · 2025Article
- Impact of liver fibrosis on AAV-mediated gene transfer to mouse hepatocytes.Nature communications · 2025Article
- Challenges in Humoral Immune Response to Adeno-Associated Viruses Determination.International journal of molecular sciences · 2025Review
- Epitope mapping using immunopeptidomics reveals novel immunodominant CD8 T cell epitopes of the AAV9 capsid.Frontiers in immunology · 2025Article
- Immunogenicity risk assessment of empty capsids present in adeno-associated viral vectors using predictive innate immune responses.Journal of pharmaceutical sciences · 2024Article
- Review
- Protein overexpression by adeno-associated virus-based gene therapy products in cardiomyocytes induces endoplasmic reticulum stress and myocardial degeneration in mice.Journal of toxicologic pathology · 2024Article
- Innate Immune Sensing of Adeno-Associated Virus Vectors.Human gene therapy · 2024Review
- Ex vivo gene editing and cell therapy for hereditary tyrosinemia type 1.Hepatology communications · 2024Article
- Prednisolone and rapamycin reduce the plasma cell gene signature and may improve AAV gene therapy in cynomolgus macaques.Gene therapy · 2024Article
7 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Recombinant adeno-associated virus (AAV) vectors have been broadly adopted as a gene delivery tool in clinical trials, owing to their high efficiency of transduction of several host tissues and their low immunogenicity. However, a considerable proportion of the population is naturally exposed to the WT virus from which AAV vectors are derived, which leads to the acquisition of immunological memory that can directly determine the outcome of gene transfer. Here, we show that prior exposure to AAV drives distinct capsid immunity profiles in healthy subjects. In peripheral blood mononuclear cells (PBMCs) isolated from AAV-seropositive donors, recombinant AAV triggered TNF-α secretion in memory CD8+ T cells, B cell differentiation into antibody-secreting cells, and anti-capsid antibody production. Conversely, PBMCs isolated from AAV-seronegative individuals appeared to carry a population of NK cells reactive to AAV. Further, we demonstrated that the AAV capsid activates IL-1β and IL-6 cytokine secretion in monocyte-related dendritic cells (moDCs). IL-1β and IL-6 blockade inhibited the anti-capsid humoral response in vitro and in vivo. These results provide insights into immune responses to AAV in humans, define a possible role for moDCs and NK cells in capsid immunity, and open new avenues for the modulation of vector immunogenicity.
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What OpenQuestion holds
Registered trials
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.