ArticleGene therapy2015
AAVrh.10 immunogenicity in mice and humans. Relevance of antibody cross-reactivity in human gene therapy.
Article in Gene therapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers, 2 of them syntheses that pooled it.
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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.
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Who cites it
55 citing papers in PubMed, 2 syntheses or guidelines pooled it, 77 citations in OpenAlex.
- Gene Therapy Advances: A Meta-Analysis of AAV Usage in Clinical Settings.Frontiers in medicine · 2021Pooled it
- T-Cell Dependent Immunogenicity of Protein Therapeutics Pre-clinical Assessment and Mitigation-Updated Consensus and Review 2020.Frontiers in immunology · 2020Pooled it
- Article
- Seroprevalence of anti-AAV antibodies in a healthy adult Spanish population: findings from the SAAVIA study.Gene therapy · 2026Article
- Immunogenicity of Gene and Cell Therapies.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2026Review
- Stem cell and gene therapies for leukodystrophies.Molecular therapy. Methods & clinical development · 2025Review
- Natural history of preexisting AAV5 antibodies in adults with hemophilia B during the lead-in of the etranacogene dezaparvovec phase 3 study.Molecular therapy. Methods & clinical development · 2025Article
- Immune Response to Bioluminescence Imaging Reporters in Murine Tumor Models.Molecular imaging and biology · 2025Article
- Gene therapy for hemophilia - From basic science to first approvals of "one-and-done" therapies.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- A dose escalation and safety study of AAVrh10-mediated Schwann cell-targeted gene therapy for CMT1X.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Article
- Inner Ear Gene Therapy: An Overview from Bench to Bedside.Molecular diagnosis & therapy · 2025Review
- Article
- Recombinant Adeno-Associated Virus Vectors for Gene Therapy of the Central Nervous System: Delivery Routes and Clinical Aspects.Biomedicines · 2024Review
- AAV Vectors Pseudotyped with Capsids from Porcine and Bovine Species Mediate In Vitro and In Vivo Gene Delivery.Viruses · 2023Article
- Validation of Anti-Adeno Associated Virus Serotype rh10 (AAVrh.10) Total and Neutralizing Antibody Immunogenicity Assays.Pharmaceutical research · 2023Article
- In-depth comparison of Anc80L65 and AAV9 retinal targeting and characterization of cross-reactivity to multiple AAV serotypes in humans.Molecular therapy. Methods & clinical development · 2023Article
- Intracerebral lentiviral ABCD1 gene therapy in an early disease onset ALD mouse model.Gene therapy · 2023Article
- Preclinical studies in Krabbe disease: A model for the investigation of novel combination therapies for lysosomal storage diseases.Molecular therapy : the journal of the American Society of Gene Therapy · 2023Review
- AAV capsid engineering identified two novel variants with improved in vivo tropism for cardiomyocytes.Molecular therapy : the journal of the American Society of Gene Therapy · 2022Article
- AAV vectors: The Rubik's cube of human gene therapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2022Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Simian adeno-associated virus (AAV) serotype rh.10 is a promising gene therapy tool, achieving safe, sustained transgene expression in the nervous system, lung, liver and heart in animal models. To date, preexisting immunity in humans has not been confirmed, though exposure is unexpected. We compared the humoral immune response with serotypes AAVrh.10 and AAV9 in mice, and AAVrh.10, AAV9 and AAV2 in 100 healthy humans. Mice, injected-intravenously, raised significantly more anti-AAV9 than anti-AAVrh.10 IgG (immunoglobulins), and sera demonstrated greater neutralizing capacity, correspondingly. Antibody cross-binding studies in mice showed negligible cross-recognition between AAVrh.10, AAV9 and AAV2. In humans, IgG prevalence against the most common human serotype, AAV2, was 72%; AAV9, 47% and AAVrh.10, a surprising, 59%. Yet, neutralizing-antibody seroprevalences were 71% for AAV2, 18% for AAV9 and 21% for AAVrh.10. Thus, most anti-AAV9 and anti-AAVrh.10 IgG were nonneutralizing. Indeed, sera generally neutralized AAV2 more strongly than AAVrh.10. Further, all samples neutralizing AAVrh.10 or AAV9 also neutralized AAV2, suggesting antibody cross-recognition. This contrasts with the results in mice, and highlights the complexity of tailoring gene therapy to minimize the immune response in humans, when multiple-mixed infections during a lifetime evoke a broad repertoire of preexisting antibodies capable of cross reacting with non-human serotypes.
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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.