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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Osada, T; Yang, XY; Hartman, ZC; Glass, O; Hodges, BL; Niedzwiecki, D; Morse, MA; Lyerly, HK; Amalfitano, A; Clay, TM

Published Date

  • September 2009

Published In

Volume / Issue

  • 16 / 9

Start / End Page

  • 673 - 682

PubMed ID

  • 19229288

Pubmed Central ID

  • 19229288

Electronic International Standard Serial Number (EISSN)

  • 1476-5500

Digital Object Identifier (DOI)

  • 10.1038/cgt.2009.17

Language

  • eng

Conference Location

  • England