ArticleGene therapy2009
Antigen-specific humoral tolerance or immune augmentation induced by intramuscular delivery of adeno-associated viruses encoding CTLA4-Ig-antigen fusion molecules.
Article in Gene therapy, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 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
3 citing papers in PubMed, 10 citations in OpenAlex.
- Teaching an old vector new tricks: the surprising versatility of AAV vaccines.Journal of virology · 2025Review
- Liver transplant tolerance and its application to the clinic: can we exploit the high dose effect?Clinical & developmental immunology · 2013Review
- Fc-fusion proteins: new developments and future perspectives.EMBO molecular medicine · 2012Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
This study initially sought to investigate the immunostimulatory properties of recombinant adeno-associated virus (rAAV) with a view to developing a genetic vaccine for malaria using muscle as a target tissue. To augment humoral immunity, the AAV-encoded antigen was genetically fused with CTLA4-Ig, a recombinant molecule that binds B7 costimulatory molecules. At 10(9) vg, CTLA4-Ig fusion promoted the humoral immune response 100-fold and was dependent on CTLA4-Ig binding with B7 costimulatory molecules, confirming plasmid DNA models using this strategy. In distinct contrast, 10(12)-10(13) vg of rAAV1 specifically induced long-lived humoral tolerance through a mechanism that is independent of CTLA4-Ig binding with B7. This finding was unexpected, as rAAV delivery to muscle, unlike liver, has shown that this tissue provides a highly immunogenic environment for induction of humoral immunity against rAAV transgene products. An additional unpredicted consequence of antigen fusion with CTLA4-Ig was the enhancement of antigen expression by approximately one log, an effect mapped to the hinge and Fc domain of IgG(1,) but not involving antigen dimerization or the neonatal Fc receptor. Collectively, these findings significantly advance the potential of rAAV both as a vaccine or immunotherapeutic platform for the induction of antigen-specific humoral immunity or tolerance and as a gene therapeutic delivery system.
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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.