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Dendritic cells transduced with an adenovirus vector encoding interleukin-12 are a potent vaccine for invasive pulmonary aspergillosis

Genes & Immunity volume 6, pages 103–114 (2005)Cite this article

Abstract

Invasive pulmonary aspergillosis (IPA) is a common and devastating pneumonia. We developed a novel antiinfective vaccine that couples the potent Ag-presenting capacity of dendritic cells (DCs) with paracrine delivery of interleukin-12 (IL-12) to local immune response sites. Our results showed that DCs engulfed Aspergillus conidia through coiling phagocytosis. Transfection of DCs with adenovirus encoding the cDNA of IL-12 did not affect their morphology and capacity to engulf conidia. The transduced DCs secreted IL-12, which was biologically active, to induce the production of gamma interferon (IFN-γ) from spleen cells. Adoptive transfer of DCs pulsed with heat-inactivated Aspergillus fumigatus (HAF) to naïve mice induced the Ag-specific production of IFN-γ; the transduced HAF-pulsed DCs augmented this immune response further. Animals receiving HAF-pulsed DCs had lower fungal burdens, a more than three-fold higher survival rate at day 3. This protection was associated with a pronounced enhancement in the Aspergillus-specific IFN-γ response. IL-12-engineered DCs augmented this protection strikingly as judged by a higher survival, and almost no Aspergillus could be detected in the lung of mice that had received IL-12-transduced HAF-pulsed DCs. These results suggest that antigen-pulsed DCs and IL-12 gene therapy could be used as adjunct therapy for aspergillosis.

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Acknowledgements

This work was supported by the Shanghai Health Care Systems (Bai Ren Project, Grant 98BR030).

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Authors and Affiliations

  1. Department of Pulmonary Medicine, Zhongshan Hospital, University of Fudan, Shanghai, China

    C Shao, J Qu, L He & H Zhou

  2. Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China

    Y Zhang, J Wang, Y Wang & X Liu

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Correspondence to J Qu.

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Shao, C., Qu, J., He, L. et al. Dendritic cells transduced with an adenovirus vector encoding interleukin-12 are a potent vaccine for invasive pulmonary aspergillosis. Genes Immun 6, 103–114 (2005). https://doi.org/10.1038/sj.gene.6364167

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