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

Cancer Gene Therapy volume 16, pages 673–682 (2009)Cite this article

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.

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Acknowledgements

This work was supported by NIH–NCI grant PO1-CA078673 to HKL and NCI P50 CA89496-01.

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Author notes

  1. A Amalfitano and T M Clay: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Surgery, Duke University Medical Center, Durham, NC, USA

    T Osada, X Y Yang, Z C Hartman, O Glass, H K Lyerly & T M Clay

  2. Prothelia Inc., Milford, MA, USA

    B L Hodges

  3. Duke Comprehensive Cancer Center, Durham, NC, USA

    D Niedzwiecki, M A Morse, H K Lyerly & T M Clay

  4. Department of Medicine, Durham, NC, USA

    M A Morse

  5. Department of Immunology, Durham, NC, USA

    H K Lyerly

  6. Department of Microbiology and Molecular Genetics and Pediatrics, Michigan State University, East Lansing, MI, USA

    A Amalfitano

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  1. T Osada
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Correspondence to T M Clay.

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Osada, T., Yang, X., Hartman, Z. et al. Optimization of vaccine responses with an E1, E2b and E3-deleted Ad5 vector circumvents pre-existing anti-vector immunity. Cancer Gene Ther 16, 673–682 (2009). https://doi.org/10.1038/cgt.2009.17

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  • DOI: https://doi.org/10.1038/cgt.2009.17

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