Evidence map›Paper›PMID 21716299›Full record

ArticleGene therapy2012

Successful attenuation of humoral immunity to viral capsid and transgenic protein following AAV-mediated gene transfer with a non-depleting CD4 antibody and cyclosporine.

J H McIntosh, M Cochrane, S Cobbold, H Waldmann, S A Nathwani, A M Davidoff, A C Nathwani

Open access · greenAbstract read
In one paragraph

Article in Gene therapy, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.

0numbers the graph read from it
0cells of the map it votes in
42citing papers in PubMed
2.6field-weighted citation impact, top 10% of its field
1 · What the graph read from 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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

42 citing papers in PubMed, 64 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Review
  5. Immunogenicity of Recombinant Adeno-Associated Virus (AAV) Vectors for Gene Transfer.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2023
    Review
  6. Article
  7. Article
  8. Review
  9. Review
  10. Article
  11. Review
  12. Review
  13. Review
  14. Immune Response Mechanisms against AAV Vectors in Animal Models.Molecular therapy. Methods & clinical development · 2020
    Review
  15. Article
  16. Article
  17. Article
  18. Article
  19. An optimized gene transfection system in WERI-Rb1 cells.International journal of molecular medicine · 2017
    Article
  20. Successful Repeated Hepatic Gene Delivery in Mice and Non-human Primates Achieved by Sequential Administration of AAV5Molecular therapy : the journal of the American Society of Gene Therapy · 2017
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 4 institutions in 2 countries.

J H McIntoshDepartment of Haematology, UCL Cancer Institute, University College London, Oxford, UK.
M Cochrane
S Cobbold
H Waldmann
S A Nathwani
A M Davidoff
A C Nathwani
University College London · GBUniversity of Oxford · GBNHS Blood and Transplant · GBSt. Jude Children's Research Hospital · US

Funding

Viral Vector Technology (VVTSR)P30CA021765 · NCI · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI CHARLES ROBERTS · 1985 to 2026
$166.9M
rAAV-Mediated Gene Therapy for Hemophillia BR01HL073838 · NHLBI · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI DAVIDOFF, ANDREW M · 2005 to 2015
$4.5M
Department of Health RP-PG-0310-1001Medical Research Council G0502121Medical Research Council G1000215NCI NIH HHS P30 CA021765NHLBI NIH HHS HL073838NHLBI NIH HHS R01 HL073838
6 · The paper itself

Abstract

The ability of transient immunosuppression with a combination of a non-depleting anti-CD4 (NDCD4) antibody and cyclosporine (CyA) to abrogate immune reactivity to both adeno-associated viral vector (AAV) and its transgene product was evaluated. This combination of immunosuppressants resulted in a 20-fold reduction in the resulting anti-AAV8 antibody titres, to levels in naïve mice, following intravenous administration of 2 × 10(12) AAV8 vector particles per kg to immunocompetent mice. This allowed efficient transduction upon secondary challenge with vector pseudotyped with the same capsid. Persistent tolerance did not result, however, as an anti-AAV8 antibody response was elicited upon rechallenge with AAV8 without immunosuppression. The route of vector administration, vector dose, AAV serotype or the concomitant administration of adenoviral vector appeared to have little impact on the ability of the NDCD4 antibody and CyA combination to moderate the primary humoral response to AAV capsid proteins. The combination of NDCD4 and CyA also abrogated the humoral response to the transgene product, that otherwise invariably would occur, following intramuscular injection of AAV5, leading to stable transgene expression. These observations could significantly improve the prospects of using rAAV vectors for chronic disorders by allowing for repeated vector administration and avoiding the development of antibodies to the transgene product.

Indexed as

Immunity, HumoralAdenoviridaeAnimalsAntibodies, ViralCapsid ProteinsCD4-Positive T-LymphocytesCyclosporineDependovirusGenetic TherapyGenetic VectorsGene Transfer TechniquesHumansImmunosuppression TherapyInjections, IntramuscularInjections, IntravenousInterferon-betaAntibodies, ViralCapsid ProteinsCyclosporineInterferon-betaRecombinant Proteins

Identifiers

PMID21716299
PMCPMC3526978
OpenAlexW1986816614

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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.