ArticleJournal of innate immunity2015
Unique Roles of TLR9- and MyD88-Dependent and -Independent Pathways in Adaptive Immune Responses to AAV-Mediated Gene Transfer.
Article in Journal of innate immunity, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers, 1 of them a synthesis that pooled it.
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
65 citing papers in PubMed, 1 synthesis or guideline pooled it, 83 citations in OpenAlex.
- rAAV immunogenicity, toxicity, and durability in 255 clinical trials: A meta-analysis.Frontiers in immunology · 2022Pooled it
- Preclinical study of an optimized AAV cancer vaccine in a spontaneous canine model of oral melanoma.Molecular therapy. Oncology · 2026Article
- Adeno-associated virus-induced neurotoxicity is prevented by CpG depletion.Molecular therapy. Advances · 2026Article
- Factor VIII originates primarily from anatomically distinct subsets of liver sinusoidal endothelial cells.Blood advances · 2026Article
- Deaths in gene therapy of Duchenne muscular dystrophy and other diseases: Underlying mechanisms and mitigating strategies.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Review
- Modulating nuclear stiffness and envelope barrier facilitates AAV nuclear entry and reduces immunogenicity.Nature communications · 2026Article
- Gene Therapy for Heart Failure: Impact on Mitochondrial Dysfunction.Biomedicines · 2026Review
- Mechanisms of and mitigating strategies for cellular immune responses to CRISPR-associated nucleases in genome editing therapy.Frontiers in medicine · 2026Review
- Pre-Existing Anti-Adeno-Associated Virus Immunity in Gene Therapy: Mechanisms, Challenges, and Potential Solutions.Human gene therapy · 2025Review
- Engineering adeno-associated viral vectors for CRISPR/Cas based in vivo therapeutic genome editing.Biomaterials · 2025Review
- Peeling back the layers of immunogenicity in Cas9-based genomic medicine.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- 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
- Use of CD19-targeted immune modulation to eradicate AAV-neutralizing antibodies.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- The curious case of AAV immunology.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Viral vectors in neurodegenerative diseases: immune responses and therapeutic applications.Frontiers in neurology · 2025Review
- Immunogenicity risk assessment of empty capsids present in adeno-associated viral vectors using predictive innate immune responses.Journal of pharmaceutical sciences · 2024Article
- Reprogramming human B cells with custom heavy-chain antibodies.Nature biomedical engineering · 2024Article
- Redundancy in Innate Immune Pathways That Promote CD8Viruses · 2024Article
- Innate Immune Sensing of Adeno-Associated Virus Vectors.Human gene therapy · 2024Review
- TLR9-independent CD8Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
5 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
Abstract
The immune system represents a significant barrier to successful gene therapy with adeno-associated viral (AAV) vectors. In particular, adaptive immune responses to the viral capsid or the transgene product are of concern. The sensing of AAV by toll-like receptors (TLRs) TLR2 and TLR9 has been suggested to play a role in innate immunity to the virus and may also shape subsequent adaptive immune responses. Here, we investigated the functions of TLR2, TLR9 and the downstream signaling adaptor MyD88 in antibody and CD8+ T-cell responses. Antibody formation against the transgene product occurred largely independently of TLR signaling following gene transfer with AAV1 or AAV2 vectors, whereas loss of signaling through the TLR9-MyD88 pathway substantially reduced CD8+ T-cell responses. In contrast, MyD88 (but neither of the TLRs) regulated antibody responses to capsid. B cell-intrinsic MyD88 was required for the formation of anti-capsid IgG2c independently of vector serotype or route of administration. However, MyD88(-/-) mice instead produced anti-capsid IgG1 that emerged with delayed kinetics but nonetheless completely prevented in vivo readministration. We conclude that there are distinct roles for TLR9 and MyD88 in promoting adaptive immune responses to AAV-mediated gene transfer and that there are redundant MyD88-dependent and MyD88-independent mechanisms that stimulate neutralizing antibody formation against AAV.
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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.