ArticleJournal of virology2008
Complement is an essential component of the immune response to adeno-associated virus vectors.
Article in Journal of virology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 116 papers.
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
116 citing papers in PubMed, 165 citations in OpenAlex.
- Clinical immunogenicity in rAAV gene therapy: Insights and implications.Molecular therapy. Advances · 2026Review
- AAV Vectors in Regenerative Medicine and Cellular Reprogramming: Potential, Pitfalls, and Specificity Constraints.International journal of molecular sciences · 2026Review
- 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
- Immunogenicity of Gene and Cell Therapies.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2026Review
- Bioengineered AAV9 and Optimised Microdystrophin Vectors Augment Phenotypic Rescue in a Murine Model of Duchenne Muscular Dystrophy.Journal of cellular and molecular medicine · 2026Article
- Adeno-Associated Virus Toxicity in Duchenne Muscular Dystrophy: Mechanisms and Clinical Considerations.Genes · 2026Review
- Gene Therapy for Heart Failure: Impact on Mitochondrial Dysfunction.Biomedicines · 2026Review
- Intravitreal AAV vector delivery induces integrin-dependent ocular inflammation, complement activation, and antiviral and DNA damage responses.Frontiers in immunology · 2026Article
- Zona pellucida-inspired smart viral vectors: a biomimetic platform for multi-modal immune evasion and triple-stimuli responsive gene delivery.Frontiers in bioengineering and biotechnology · 2026Article
- Development of a gene-activated matrix for enhanced AAV gene deliveryFrontiers in bioengineering and biotechnology · 2026Article
- Pre-Existing Anti-Adeno-Associated Virus Immunity in Gene Therapy: Mechanisms, Challenges, and Potential Solutions.Human gene therapy · 2025Review
- Emerging Technologies Tackling Adeno-Associated Viruses (AAV) Immunogenicity in Gene Therapy Applications.Pharmaceutics · 2025Review
- AAV microdystrophin gene replacement therapy for Duchenne muscular dystrophy: progress and prospects.Gene therapy · 2025Review
- 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
- Complement activation in a phase Ib study of fordadistrogene movaparvovec for Duchenne muscular dystrophy.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Use of CD19-targeted immune modulation to eradicate AAV-neutralizing antibodies.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Mechanisms of AAV neutralization by human alpha-defensins.PLoS pathogens · 2025Article
- Investigating the Immunogenic Potential of Variations in Host Cell Protein Levels in Clinical-Grade AAV8 Products.Investigative ophthalmology & visual science · 2025Article
- Emerging Thrombotic Disorders Associated with Virus-Based Innovative Therapies: From VITT to AAV Gene Therapy-Related Thrombotic Microangiopathy.Thrombosis and haemostasis · 2025Review
56 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 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Adeno-associated virus (AAV) vectors are associated with relatively mild host immune responses in vivo. Although AAV induces very weak innate immune responses, neutralizing antibodies against the vector capsid and transgene still occur. To understand further the basis of the antiviral immune response to AAV vectors, studies were performed to characterize AAV interactions with macrophages. Primary mouse macrophages and human THP-1 cells transduced in vitro using an AAV serotype 2 (AAV2) vector encoding green fluorescent protein did not result in measurable transgene expression. An assessment of internalized vector genomes showed that AAV2 vector uptake was enhanced in the presence of normal but not heat-inactivated or C3-depleted mouse/human serum. Enhanced uptake in the presence of serum coincided with increased macrophage activation as determined by the expression of NF-kappaB-dependent genes such as macrophage inflammatory protein 2 (MIP-2), interleukin-1beta (IL-1beta), IL-8, and MIP-1beta. AAV vector serotypes 1 and 8 also activated human and mouse macrophages in a serum-dependent manner. Immunoprecipitation studies demonstrated the binding of iC3b complement protein to the AAV2 capsid in human serum. AAV2 did not activate the alternative pathway of the complement cascade and lacked cofactor activity for factor I-mediated degradation of C3b to iC3b. Instead, our results suggest that the AAV capsid also binds complement regulatory protein factor H. In vivo, complement receptor 1/2- and C3-deficient mice displayed impaired humoral immunity against AAV2 vectors, with a delay in antibody development and significantly lower neutralizing antibody titers. These results show that the complement system is an essential component of the host immune response to AAV.
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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.