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Evaluation of cross-reactive cell-mediated immune responses among human, bovine and porcine adenoviruses

Gene Therapy volume 17, pages 634–642 (2010)Cite this article

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Abstract

The absence of preexisting immunity against porcine adenovirus (Ad) serotype 3 (PAd3) and bovine Ad serotype 3 (BAd3) in humans makes them attractive alternatives to human Ad serotype 5 (HAd5) vectors. To determine whether there is significant cross-reactivity among HAd5, BAd3 and PAd3 at the level of cell-mediated immune responses, BALB/c mice were inoculated intraperitoneally with wild-type (WT) or replication-defective (RD) HAd5, BAd3 or PAd3. After 35 days of the first inoculation, cross-reactive CD8+ cytotoxic T cells, as well as CD4+ Th1- and Th2-helper T cells, in the spleen were analyzed by enzyme-linked-immunospot, flow cytometry and cytotoxic T lymphocyte assays. Virus-neutralization assays were used to evaluate humoral cross-reactivity. CD8+ or CD4+ T cells primed with WT or RD HAd5, PAd3 or BAd3 showed significant (P<0.005) reactivity with homologous Ad antigens, whereas only minimal cross-reactivity was observed on stimulation with heterologous Ad antigens. Ad-neutralizing antibodies were found to be homologous Ad specific. Overall, these results suggest that there is no significant immunological cross-reactivity among HAd5, BAd3 and PAd3, thereby supporting the rationale for the use of BAd3 and PAd3 as alternative HAd vectors to circumvent anti-HAd immunity in humans.

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Acknowledgements

This work was supported by Public Health Service grant CA110176 from the National Cancer Institute. We are thankful to Jane Kovach for her excellent secretarial assistance and Ching-Yun Chang for help with statistical analyses.

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  1. D S Bangari

    Present address: 4Current address: Department of Pathology, Genzyme Corporation, 5 Mountain Road, Framingham, MA, USA,

Authors and Affiliations

  1. Department of Comparative Pathobiology, School of Veterinary Medicine, Purdue University, West Lafayette, IN, USA

    A Sharma, M Tandon, Y S Ahi, D S Bangari, R Vemulapalli & S K Mittal

  2. Bindley Bioscience Center, Purdue University, West Lafayette, IN, USA

    A Sharma, M Tandon, Y S Ahi & S K Mittal

  3. Animal Disease Diagnostic Laboratory, Purdue University, West Lafayette, IN, USA,

    R Vemulapalli

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Correspondence to S K Mittal.

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Sharma, A., Tandon, M., Ahi, Y. et al. Evaluation of cross-reactive cell-mediated immune responses among human, bovine and porcine adenoviruses. Gene Ther 17, 634–642 (2010). https://doi.org/10.1038/gt.2010.1

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