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

C. Shao, Jiemingqu Qu, L. He, Y. Zhang, J. Wang, H. Zhou, Y. Wang, X. Liu

Research output: Contribution to journalArticlepeer-review

35 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)103-114
Number of pages12
JournalGenes and Immunity
Volume6
Issue number2
DOIs
StatePublished - Mar 2005
Externally publishedYes

Keywords

  • Adenovirus
  • Dendritic cells
  • Gene therapy
  • Invasive pulmonary aspergillosis

ASJC Scopus subject areas

  • Immunology
  • Genetics
  • Genetics(clinical)

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