Optimization of vaccine responses with an E1, E2b and E3-deleted Ad5 vector circumvents pre-existing anti-vector immunity View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2009-09

AUTHORS

Takuya Osada, Xiao Yi Yang, Zachary C. Hartman, Oliver Glass, Bradley L. Hodges, Donna Niedzwiecki, Michael A. Morse, H. Kim Lyerly, Andrea Amalfitano, Timothy M. Clay

ABSTRACT

Recombinant serotype 5 adenovirus (Ad5) vectors lacking E1 expression induce robust immune responses against encoded transgenes in pre-clinical models, but have muted responses in human trials because of widespread pre-existing anti-adenovirus immunity. Attempts to circumvent Ad5-specific immunity by using alternative serotypes or modifying capsid components have not yielded profound clinical improvement. To address this issue, we explored a novel alternative strategy, specifically reducing the expression of structural Ad5 genes by creating E1 and E2b deleted recombinant Ad5 vectors. Our data show that [E1-, E2b-]vectors retaining the Ad5 serotype are potent immunogens in pre-clinical models despite the presence of significant Ad5-specific immunity, in contrast to [E1-] vectors. These pre-clinical studies with E1 and E2b-deleted recombinant Ad5 vectors suggest that anti-Ad immunity will no longer be a limiting factor, and that clinical trials to evaluate their performance are warranted. More... »

PAGES

cgt200917

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/cgt.2009.17

DOI

http://dx.doi.org/10.1038/cgt.2009.17

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1033355030

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/19229288


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Turtle is a human-readable linked data format.

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RDF/XML is a standard XML format for linked data.

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