Dendritic cells transduced with an adenovirus vector encoding interleukin-12 are a potent vaccine for invasive pulmonary aspergillosis.
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-gamma) from spleen cells. Adoptive transfer of DCs pulsed with heat-inactivated Aspergillus fumigatus (HAF) to naive mice induced the Ag-specific production of IFN-gamma; 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-gamma 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.
Shao
C
C
Department of Pulmonary Medicine, Zhongshan Hospital, University of Fudan, Shanghai, China.
Qu
J
J
He
L
L
Zhang
Y
Y
Wang
J
J
Zhou
H
H
Wang
Y
Y
Liu
X
X
D000256:Adenoviridae / Q000235:genetics; D019264:Adoptive Transfer; D000818:Animals; D001229:Aspergillosis, Allergic Bronchopulmonary / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control; D001232:Aspergillus fumigatus / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology* / Q000637:transplantation / Q000648:ultrastructure; D005657:Fungal Vaccines / Q000235:genetics / Q000276:immunology*; D015316:Genetic Therapy; D018664:Interleukin-12 / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C
D005657:Fungal Vaccines; D018664:Interleukin-12