title: Coexpression of interleukin-12 chains by a self-splicing vector increases the protective cellular immune response of DNA and Mycobacterium bovis BCG vaccines against Mycobacterium tuberculosis.
abstract: More effective vaccines against Mycobacterium tuberculosis may contribute to the control of this major human pathogen. DNA vaccines encoding single mycobacterial proteins stimulate antimycobacterial T-cell responses and induce partial protection against M. tuberculosis in animal models. The protective efficacy of these vaccines encoding a single antigen, however, has been less than that afforded by the current vaccine, Mycobacterium bovis bacillus Calmette-Guérin (BCG). The heterodimeric cytokine interleukin-12 (IL-12) potentiates the induction and maintenance of the type 1 helper T-cell response. We have developed a novel self-splicing vector based on the 2A protein of foot-and-mouth disease virus that permits the coordinate expression of both chains of IL-12 (p2AIL12). Coimmunization with this vector and DNA expressing M. tuberculosis antigen 85B or MPT64 enhanced the specific lymphocyte proliferative response and increased the frequency of specific gamma interferon-secreting T cells against the whole protein and a defined CD8(+) T-cell epitope on MPT64. Further, coimmunizing with p2AIL12 significantly increased the protective efficacy of DNA-85 in the lung against an aerosol challenge with M. tuberculosis to the level achieved with BCG. Therefore, codelivery of an IL-12-secreting plasmid may be a potent strategy for enhancing the protective efficacy of vaccines against M. tuberculosis.
authors.affiliation: Centenary Institute of Cancer Medicine and Cell Biology, Newtown, New South Wales 2042, Australia.
authors.forename: Umaimainthan
authors.initials: U
authors.lastname: Palendira
authors.forename: Arun T
authors.initials: AT
authors.lastname: Kamath
authors.forename: Carl G
authors.initials: CG
authors.lastname: Feng
authors.forename: Ela
authors.initials: E
authors.lastname: Martin
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Chaplin
authors.forename: James A
authors.initials: JA
authors.lastname: Triccas
authors.forename: Warwick J
authors.initials: WJ
authors.lastname: Britton
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D001500:BCG Vaccine / Q000276:immunology*; D005260:Female; D005822:Genetic Vectors; D018664:Interleukin-12 / Q000235:genetics* / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D013601:T-Lymphocytes / Q000276:immunology; D019444:Vaccines, DNA / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000276:immunology*; D014764:Viral Proteins / Q000276:immunology
chemical_list: D000907:Antibodies, Bacterial; D001500:BCG Vaccine; D019444:Vaccines, DNA; D014614:Vaccines, Synthetic; D014764:Viral Proteins; C057421:virus protein 2A; D018664:Interleukin-12