title: Plasmid interleukin-23 (IL-23), but not plasmid IL-27, enhances the protective efficacy of a DNA vaccine against Mycobacterium tuberculosis infection.
abstract: 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.
authors.affiliation: Centenary Institute of Cancer Medicine and Cell Biology, Mycobacterial Research Laboratory, Locked Bag No. 6, Newtown, NSW 2042, Australia.
authors.forename: Teresa M
authors.initials: TM
authors.lastname: Wozniak
authors.forename: Anthony A
authors.initials: AA
authors.lastname: Ryan
authors.forename: James A
authors.initials: JA
authors.lastname: Triccas
authors.forename: Warwick J
authors.initials: WJ
authors.lastname: Britton
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000235:genetics; D000595:Amino Acid Sequence; D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis; D000942:Antigens, Bacterial / Q000276:immunology; D002460:Cell Line; D003713:Dendritic Cells / Q000378:metabolism / Q000382:microbiology; D005260:Female; D005822:Genetic Vectors; D006801:Humans; D018664:Interleukin-12 / Q000502:physiology; D053759:Interleukin-23; D053760:Interleukin-23 Subunit p19; D007378:Interleukins / Q000008:administration & dosage / Q000235:genetics* / Q000502:physiology; D051379:Mice; D008969:Molecular Sequence Data; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D010957:Plasmids; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D014162:Transfection; D032581:Tuberculosis Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D014397:Tuberculosis, Pulmonary / Q000276:immunology* / Q000517:prevention & control; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; C508840:IL23A protein, human; C508841:Il23a protein, mouse; C486767:Il27 protein, mouse; D053759:Interleukin-23; D053760:Interleukin-23 Subunit p19; D007378:Interleukins; D032581:Tuberculosis Vaccines; D019444:Vaccines, DNA; D018664:Interleukin-12