ArticleJournal of virology2009
Cytotoxic-T-lymphocyte-mediated elimination of target cells transduced with engineered adeno-associated virus type 2 vector in vivo.
Article in Journal of virology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 1 of them a synthesis that pooled 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.
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
31 citing papers in PubMed, 1 synthesis or guideline pooled it, 42 citations in OpenAlex.
- A systematic review of immunosuppressive protocols used in AAV gene therapy for monogenic disorders.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Pooled it
- Immune Response Associated Hepatotoxicity in Hemophilia Gene Therapy: Mechanisms, Management, and Challenges.Journal of hematology · 2026Review
- Assessment of Immune Responses Against AAV Encoded Transgene Products.The AAPS journal · 2026Review
- Neo-antigen tumor vaccination depends on CD4-licensing conveyed by adeno-associated virus like particles.Molecular therapy : the journal of the American Society of Gene Therapy · 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
- The combination of rAAV pseudo-lipid nanoparticle and triamcinolone acetonide enables multi-administration to liver.Molecular therapy. Methods & clinical development · 2025Article
- Single-shot AAV-vectored vaccine against SARS-CoV-2 with fast and long-lasting immunity.Acta pharmaceutica Sinica. B · 2023Article
- Immunological barriers to haematopoietic stem cell gene therapy.Nature reviews. Immunology · 2022Review
- A versatile toolkit for overcoming AAV immunity.Frontiers in immunology · 2022Review
- Adeno-Associated Viruses (AAV) and Host Immunity - A Race Between the Hare and the Hedgehog.Frontiers in immunology · 2021Review
- T Cell-Mediated Immune Responses to AAV and AAV Vectors.Frontiers in immunology · 2021Review
- Bound Protein- and Peptide-Based Strategies for Adeno-Associated Virus Vector-Mediated Gene Therapy: Where Do We Stand Now?Human gene therapy · 2020Article
- Timing of Intensive Immunosuppression Impacts Risk of Transgene Antibodies after AAV Gene Therapy in Nonhuman Primates.Molecular therapy. Methods & clinical development · 2020Article
- Translational Potential of Immune Tolerance Induction by AAV Liver-Directed Factor VIII Gene Therapy for Hemophilia A.Frontiers in immunology · 2020Review
- Serotype survey of AAV gene delivery via subconjunctival injection in mice.Gene therapy · 2018Article
- Inhibition of antigen presentation during AAV gene therapy using virus peptides.Human molecular genetics · 2018Article
- Efficient Capsid Antigen Presentation From Adeno-Associated Virus Empty VirionsFrontiers in immunology · 2018Article
- An Immune-Competent Murine Model to Study Elimination of AAV-Transduced Hepatocytes by Capsid-Specific CD8Molecular therapy. Methods & clinical development · 2017Article
- Antigenic and immunosuppressive properties of a trimeric recombinant transmembrane envelope protein gp41 of HIV-1.PloS one · 2017Article
- Adeno-Associated Virus Gene Therapy for Liver Disease.Human gene therapy · 2016Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
A recent clinical trial in patients with hemophilia B has suggested that adeno-associated virus (AAV) capsid-specific cytotoxic T lymphocytes (CTLs) eliminated AAV-transduced hepatocytes and resulted in therapeutic failure. AAV capsids elicit a CTL response in animal models; however, these capsid-specific CTLs fail to kill AAV-transduced target cells in mice. To better model the human clinical trial data in mice, we introduced an immunodominant epitope derived from ovalbumin (OVA; SIINFEKL) into the AAV capsid and tested CTL-mediated killing of AAV2-transduced target tissues in vivo. Initially, in vitro experiments demonstrated both classical class I and cross-presentation of the OVA antigen, following endogenous expression or AAV2-OVA vector transduction, respectively. Furthermore, an OVA-specific CTL response was elicited after muscular or systemic injection of the AAV2-OVA vector. Finally, CTL reactivity was enhanced in mice with established SIINFEKL-specific immunity after AAV2-OVA/alpha1 anti-trypsin (AAT) administration. Most importantly, these OVA-specific CTLs decreased AAT expression in mice treated with AAV2-OVA/AAT vector that followed a time course mimicking uncoating kinetics of AAV2 transduction in OVA-immunized mice. These results demonstrate that AAV capsid-derived antigens elicit CD8(+) CTL reactivity, and these CTLs eliminated AAV-transduced target cells in mice. Notably, this model system can be exploited to study the kinetics of capsid presentation from different serotypes of AAV and permit the design of novel strategies to block CTL-mediated killing of AAV-transduced cells.
Indexed as
Identifiers
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.