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Infection and Immunity, June 1999, p. 2996-3001, Vol. 67, No. 6
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Construction of a Single-Chain Interleukin-12-Expressing Retroviral Vector and Its Application in Cytokine Gene Therapy against Experimental Coccidioidomycosis

Chengyong Jiang,* D. Mitchell Magee, and Rebecca A. Cox

Department of Clinical Investigation, Texas Center for Infectious Disease, San Antonio, Texas 78223

Received 6 January 1999/Returned for modification 20 February 1999/Accepted 24 March 1999

T-cell-mediated immunity is an important determinant in protection against primary infection with Coccidioides immitis, a dimorphic fungal pathogen that causes the disease coccidioidomycosis. To determine if interleukin-12 (IL-12) gene therapy could potentiate host response against C. immitis, we constructed a single-chain cDNA encoding the p40 and p35 subunits linked by a polylinker and, using a retroviral vector, transfected J774 macrophages with the construct. The transduced J774 cells expressed IL-12 in vitro, with a mean concentration of 28,440 pg from 106 cells in 48 h as measured by an IL-12 (p75)-specific enzyme-linked immunosorbent assay. The secreted IL-12 was biologically active, as judged by its ability to induce the production of gamma interferon (IFN-gamma ) by spleen cells from BALB/c mice. Treatment of the highly susceptible BALB/c mouse strain with the IL-12-transduced J774 cells inhibited C. immitis growth in tissues from mice challenged by a pulmonary route, as evidenced by 1.37-, 2.59-, and 1.22-log reductions in the number of CFU in the lungs, spleens, and livers, respectively, compared to the fungal load in mice given vector-transduced J774 cells. The protective effect of IL-12 gene therapy was accompanied by increased levels of IFN-gamma in the lungs and sera of mice treated with IL-12-transduced J774 cells and the constitutive production of IFN-gamma by their spleen cells cultured in vitro. These results suggest that IL-12 gene therapy could be used as adjunct therapy for coccidioidomycosis.

* Corresponding author. Mailing address: Dept. of Clinical Investigation, Texas Center for Infectious Disease, 2303 SE Military Dr., San Antonio, TX 78223. Phone: (210) 534-8857. Fax: (210) 531-4550. E-mail: chengyong.jiang{at}tdh.state.tx.us.

Infection and Immunity, June 1999, p. 2996-3001, Vol. 67, No. 6
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Cox, R. A., Magee, D. M. (2004). Coccidioidomycosis: Host Response and Vaccine Development. Clin. Microbiol. Rev. 17: 804-839 [Abstract] [Full Text]  
  • Bermudez-Humaran, L. G., Langella, P., Cortes-Perez, N. G., Gruss, A., Tamez-Guerra, R. S., Oliveira, S. C., Cardenas, O. S., Montes de Oca-Luna, R., Le Loir, Y. (2003). Intranasal Immunization with Recombinant Lactococcus lactis Secreting Murine Interleukin-12 Enhances Antigen-Specific Th1 Cytokine Production. Infect. Immun. 71: 1887-1896 [Abstract] [Full Text]  
  • Jiang, C., Magee, D. M., Ivey, F. D., Cox, R. A. (2002). Role of Signal Sequence in Vaccine-Induced Protection against Experimental Coccidioidomycosis. Infect. Immun. 70: 3539-3545 [Abstract] [Full Text]  
  • Jiang, C., Magee, D. M., Cox, R. A. (1999). Coadministration of Interleukin 12 Expression Vector with Antigen 2 cDNA Enhances Induction of Protective Immunity against Coccidioides immitis. Infect. Immun. 67: 5848-5853 [Abstract] [Full Text]  


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