Open AccessPlasmid Interleukin-23 (IL-23), but Not Plasmid IL-27, Enhances the Protective Efficacy of a DNA Vaccine againstMycobacterium tuberculosisInfection
Author(s) -
Teresa M. Wozniak,
Anthony A. Ryan,
James A. Triccas,
Warwick J. Britton
Publication year - 2006
Publication title -
infection and immunity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.508
H-Index - 220
eISSN - 1070-6313
pISSN - 0019-9567
DOI - 10.1128/iai.74.1.557-565.2006
Subject(s) - biology , mycobacterium tuberculosis , interleukin 12 , dna vaccination , plasmid , microbiology and biotechnology , interleukin 4 , transfection , antigen , tuberculosis vaccines , t cell , mycobacterium bovis , immune system , tuberculosis , immunology , cytotoxic t cell , cell culture , immunization , in vitro , dna , medicine , biochemistry , genetics , pathology
Protection against intracellular pathogens such asMycobacterium 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 againstM. 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 strainMycobacterium bovis bacille Calmette-Guérin (BCG), and no significant upregulation of IL-27 was observed. Coimmunization of C57BL/6 mice with DNA expressingM. tuberculosis antigen 85B (Ag85B; DNA85B) and plasmids expressing IL-23 or IL-12 stimulated stronger Ag85B-specific T-cell proliferative and IFN-γ 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 aerosolM. tuberculosis challenge. Therefore, both p2AIL-23 and p2AIL-12 are valuable as cytokine adjuvants for increasing the protective antituberculosis immunity induced by DNA vaccines.