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Infection and Immunity, January 2006, p. 557-565, Vol. 74, No. 1
0019-9567/06/$08.00+0     doi:10.1128/IAI.74.1.557-565.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Plasmid Interleukin-23 (IL-23), but Not Plasmid IL-27, Enhances the Protective Efficacy of a DNA Vaccine against Mycobacterium tuberculosis Infection

Teresa M. Wozniak,1 Anthony A. Ryan,1 James A. Triccas,1,2 and Warwick J. Britton1,2*

Mycobacterial Research Group, Centenary Institute of Cancer Medicine and Cell Biology, Locked Bag No. 6, Newtown, NSW 2042, Australia,1 Department of Medicine, University of Sydney, Sydney, NSW 2006, Australia2

Received 21 June 2005/ Returned for modification 25 July 2005/ Accepted 23 September 2005

Protection against intracellular pathogens such as Mycobacterium tuberculosis requires the development of Th1-like T-cell responses. This in turn is dependent on the pattern of cytokine produced from dendritic cells (DCs) after infection. Three heterodimeric cytokines, interleukin-12 (IL-12), IL-23, and IL-27, as well as IL-18, contribute to the differentiation and expansion of naive CD4+ T cells. In this study we compared the effects of plasmids expressing both chains of IL-12, IL-23, or IL-27 as adjuvants for DNA immunization against M. tuberculosis infection. The genes encoding p19 and p40 chains of IL-23 or EBI3 and p28 chains of IL-27 were cloned on either side of a self-cleaving peptide from the FMDV2A protein. The secretion of functional cytokines from transfected cells was detected with bioassays. Supernatant from p2AIL-23-transfected cells induced the release of IL-17 from activated lymphocytes, confirming the presence of bioactive IL-23. Further, supernatant from p2AIL-27-transfected cells stimulated a significant increase in the proliferation of peptide-stimulated transgenic CD4+ T cells. In initial experiments, M. tuberculosis infection of DCs was more potent at inducing IL-12 and IL-23 secretion than infection with the vaccine strain Mycobacterium bovis bacille Calmette-Guérin (BCG), and no significant upregulation of IL-27 was observed. Coimmunization of C57BL/6 mice with DNA expressing M. tuberculosis antigen 85B (Ag85B; DNA85B) and plasmids expressing IL-23 or IL-12 stimulated stronger Ag85B-specific T-cell proliferative and IFN-{gamma} responses than DNA85B alone, whereas the addition of p2AIL-27 had no effect. Interestingly, DNA85B codelivered with p2AIL-12, but not p2AIL-23, reduced the immunoglobulin G antibody response. Both p2AIL-23 and p2AIL-12, but not p2AIL-27, enhanced the protective efficacy of DNA85B against aerosol M. tuberculosis challenge. Therefore, both p2AIL-23 and p2AIL-12 are valuable as cytokine adjuvants for increasing the protective antituberculosis immunity induced by DNA vaccines.

* Corresponding author. Mailing address: Centenary Institute of Cancer Medicine and Cell Biology, Mycobacterial Research Laboratory, Locked Bag No. 6, Newtown, NSW 2042, Australia. Phone: (612) 9515-5210. Fax: (612) 9351-3968. E-mail: wbritton{at}med.usyd.edu.au.

Editor: D. L. Burns

Infection and Immunity, January 2006, p. 557-565, Vol. 74, No. 1
0019-9567/06/$08.00+0     doi:10.1128/IAI.74.1.557-565.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

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