TY - JOUR
T1 - Efficacy of antigen 2/proline-rich antigen cDNA-transfected dendritic cells in immunization of mice against Coccidioides posadasii
AU - Awasthi, Shanjana
AU - Awasthi, Vibhudutta
AU - Magee, Dewey
AU - Coalson, Jacqueline J.
N1 - Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 2005/9/15
Y1 - 2005/9/15
N2 - Coccidioides posadasii causes coccidiodomycosis, or Valley fever, in the endemic regions of the Southwestern United States. The susceptibility to C. posadasii infection has been attributed to a decreased Th1 cellular response. APCs, especially dendritic cells (DCs), play an important role in the activation of Th1 response. In this study, we investigated the efficacy of a DC-based vaccine against C. posadasii in a mouse model of coccidioidomycosis. We intranasally immunized C57BL6 mice with syngeneic, bone marrow-derived DCs (JAWS II cells) transfccted with a cDNA encoding the protective Coccidiodes-Ag2/ proline-rich Ag. The immunized mice were lethally challenged with C. posadasii through either an i.p. or intranasal route. Upon necropsy after 10 days of infection, fungal burden in lung and spleen of immunized mice was significantly reduced as compared with the control animals. The lung tissue homogenates of immunized animals showed higher levels of IFN-γ. Histologically, lung tissues of immunized mice were in better condition than the control mice. To further investigate, we studied the biodistribution and trafficking of injected DCs by nuclear imaging techniques. For this purpose, the transfected DCs were radiolabeled with 111In-oxime. Scintigraphic images showed that most of the label remained in the gastrointestinal tract. A significant amount was also observed in lung, but there were negligible circulating 111In label in blood. The results suggest that the DCs have a potent immunostimulatory activity, and immunization with DCs transfected with Ag2/proline-rich Ag-cDNA induces protective immunity against C. posadasii in C57BL6 mice.
AB - Coccidioides posadasii causes coccidiodomycosis, or Valley fever, in the endemic regions of the Southwestern United States. The susceptibility to C. posadasii infection has been attributed to a decreased Th1 cellular response. APCs, especially dendritic cells (DCs), play an important role in the activation of Th1 response. In this study, we investigated the efficacy of a DC-based vaccine against C. posadasii in a mouse model of coccidioidomycosis. We intranasally immunized C57BL6 mice with syngeneic, bone marrow-derived DCs (JAWS II cells) transfccted with a cDNA encoding the protective Coccidiodes-Ag2/ proline-rich Ag. The immunized mice were lethally challenged with C. posadasii through either an i.p. or intranasal route. Upon necropsy after 10 days of infection, fungal burden in lung and spleen of immunized mice was significantly reduced as compared with the control animals. The lung tissue homogenates of immunized animals showed higher levels of IFN-γ. Histologically, lung tissues of immunized mice were in better condition than the control mice. To further investigate, we studied the biodistribution and trafficking of injected DCs by nuclear imaging techniques. For this purpose, the transfected DCs were radiolabeled with 111In-oxime. Scintigraphic images showed that most of the label remained in the gastrointestinal tract. A significant amount was also observed in lung, but there were negligible circulating 111In label in blood. The results suggest that the DCs have a potent immunostimulatory activity, and immunization with DCs transfected with Ag2/proline-rich Ag-cDNA induces protective immunity against C. posadasii in C57BL6 mice.
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U2 - 10.4049/jimmunol.175.6.3900
DO - 10.4049/jimmunol.175.6.3900
M3 - Article
C2 - 16148136
AN - SCOPUS:24744467809
SN - 0022-1767
VL - 175
SP - 3900
EP - 3906
JO - Journal of Immunology
JF - Journal of Immunology
IS - 6
ER -