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

Cancer Gene Ther. 2009 Sep;16(9):673-82. doi: 10.1038/cgt.2009.17. Epub 2009 Feb 20.


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adenoviridae / genetics*
  • Adenoviridae / immunology*
  • Adenovirus E1 Proteins / genetics*
  • Adenovirus E1 Proteins / immunology
  • Adenovirus E2 Proteins / genetics*
  • Adenovirus E2 Proteins / immunology
  • Adenovirus E3 Proteins / genetics*
  • Adenovirus E3 Proteins / immunology
  • Animals
  • Antigen Presentation
  • Cancer Vaccines / genetics
  • Cancer Vaccines / immunology*
  • Carcinoembryonic Antigen / metabolism
  • Cell Differentiation
  • Cells, Cultured
  • Cytotoxicity, Immunologic
  • Dendritic Cells / cytology
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism
  • Gene Deletion
  • Genetic Vectors / immunology*
  • Humans
  • Killer Cells, Natural / immunology
  • Kinetics
  • Mice
  • Mice, Inbred C57BL


  • Adenovirus E1 Proteins
  • Adenovirus E2 Proteins
  • Adenovirus E3 Proteins
  • Cancer Vaccines
  • Carcinoembryonic Antigen