Efficacy of antigen 2/proline-rich antigen cDNA-transfected dendritic cells in immunization of mice against Coccidioides posadasii

Shanjana Awasthi, Vibhudutta Awasthi, Dewey Magee, Jacqueline J. Coalson

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)3900-3906
Number of pages7
JournalJournal of Immunology
Volume175
Issue number6
StatePublished - Sep 15 2005

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Coccidioides
Proline
Dendritic Cells
Immunization
Complementary DNA
Antigens
Coccidioidomycosis
Lung
Southwestern United States
Oximes
Mycoses
Gastrointestinal Tract
Immunity
Vaccines
Spleen
Bone Marrow
Infection

ASJC Scopus subject areas

  • Immunology

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Efficacy of antigen 2/proline-rich antigen cDNA-transfected dendritic cells in immunization of mice against Coccidioides posadasii. / Awasthi, Shanjana; Awasthi, Vibhudutta; Magee, Dewey; Coalson, Jacqueline J.

In: Journal of Immunology, Vol. 175, No. 6, 15.09.2005, p. 3900-3906.

Research output: Contribution to journalArticle

Awasthi, Shanjana ; Awasthi, Vibhudutta ; Magee, Dewey ; Coalson, Jacqueline J. / Efficacy of antigen 2/proline-rich antigen cDNA-transfected dendritic cells in immunization of mice against Coccidioides posadasii. In: Journal of Immunology. 2005 ; Vol. 175, No. 6. pp. 3900-3906.
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abstract = "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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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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