ArticleMolecular therapy : the journal of the American Society of Gene Therapy2013
Modulation of CD8+ T cell responses to AAV vectors with IgG-derived MHC class II epitopes.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 1 of them a synthesis that pooled it.
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Who cites it
27 citing papers in PubMed, 1 synthesis or guideline pooled it, 42 citations in OpenAlex.
- T-Cell Dependent Immunogenicity of Protein Therapeutics Pre-clinical Assessment and Mitigation-Updated Consensus and Review 2020.Frontiers in immunology · 2020Pooled it
- Immune Tolerance-Adjusted Personalized Immunogenicity Prediction for Pompe Disease.Frontiers in immunology · 2021Trial
- The curious case of AAV immunology.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Epitope mapping using immunopeptidomics reveals novel immunodominant CD8 T cell epitopes of the AAV9 capsid.Frontiers in immunology · 2025Article
- Adeno-Associated Virus Engineering and Load Strategy for Tropism Modification, Immune Evasion and Enhanced Transgene Expression.International journal of nanomedicine · 2024Review
- AAV Immunotoxicity: Implications in Anti-HBV Gene Therapy.Microorganisms · 2023Review
- Adeno-associated virus-9 reverses delayed gastric emptying of solids in diabetic mice.Neurogastroenterology and motility · 2023Article
- Immunogenicity of Recombinant Adeno-Associated Virus (AAV) Vectors for Gene Transfer.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2023Review
- A SARS-CoV-2 NSP7 homolog of a Treg epitope suppresses CD4+ and CD8+ T cell memory responses.Frontiers in immunology · 2023Article
- The HLA class I immunopeptidomes of AAV capsid proteins.Frontiers in immunology · 2023Article
- Adeno-Associated Viruses (AAV) and Host Immunity - A Race Between the Hare and the Hedgehog.Frontiers in immunology · 2021Review
- Tregitopes Improve Asthma by Promoting Highly Suppressive and Antigen-Specific Tregs.Frontiers in immunology · 2021Article
- Adeno-associated viral vector-mediated immune responses: Understanding barriers to gene delivery.Pharmacology & therapeutics · 2020Review
- Therapeutic administration of Tregitope-Human Albumin Fusion with Insulin Peptides to promote Antigen-Specific Adaptive Tolerance Induction.Scientific reports · 2019Article
- Antigen-selective modulation of AAV immunogenicity with tolerogenic rapamycin nanoparticles enables successful vector re-administration.Nature communications · 2018Article
- Promise of adeno-associated virus as a gene therapy vector for cardiovascular diseases.Heart failure reviews · 2017Review
- Application of polyploid adeno-associated virus vectors for transduction enhancement and neutralizing antibody evasion.Journal of controlled release : official journal of the Controlled Release Society · 2017Article
- The impact of the immune system on the safety and efficiency of enzyme replacement therapy in lysosomal storage disorders.Journal of inherited metabolic disease · 2016Review
- Recent Developments in Gene Therapy for Homozygous Familial Hypercholesterolemia.Current atherosclerosis reports · 2016Review
- Treatment of multifocal breast cancer by systemic delivery of dual-targeted adeno-associated viral vectors.Gene therapy · 2015Article
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Authors and funding
15 authors at 6 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Immune responses directed against viral capsid proteins constitute a main safety concern in the use of adeno-associated virus (AAV) as gene transfer vectors in humans. Pharmacological immunosuppression has been proposed as a solution to the problem; however, the approach suffers from several potential limitations. Using MHC class II epitopes initially identified within human IgG, named Tregitopes, we showed that it is possible to modulate CD8+ T cell responses to several viral antigens in vitro. We showed that incubation of peripheral blood mononuclear cells with these epitopes triggers proliferation of CD4+CD25+FoxP3+ T cells that suppress killing of target cells loaded with MHC class I antigens in an antigen-specific fashion, through a mechanism that seems to require cell-to-cell contact. Expression of a construct encoding for the AAV capsid structural protein fused to Tregitopes resulted in reduction of CD8+ T cell reactivity against the AAV capsid following immunization with an adenoviral vector expressing capsid. This was accompanied by an increase in frequency of CD4+CD25+FoxP3+ T cells in spleens and lower levels of inflammatory infiltrates in injected tissues. This proof-of-concept study demonstrates modulation of CD8+ T cell reactivity to an antigen using regulatory T cell epitopes is possible.
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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.