title: Th1-biased immune responses induced by DNA-based immunizations are mediated via action on professional antigen-presenting cells to up-regulate IL-12 production.
abstract: The efficacy of DNA-based immunization in conferring protective immunity against certain microbial pathogens including human immunodeficiency virus type 1 (HIV-1) has been described. The potential advantage of DNA-based immunization over the traditional vaccines largely results from its capacity to efficiently induce Th1-biased immune responses against an encoded antigen. We describe how Th1-biased immune responses are induced by DNA-based immunization, using a DNA vaccine construct encoding HIV-1 gp160 cDNA and an eukaryotic expression plasmid carrying murine IFN-gamma cDNA. Transfection of an eukaryotic expression plasmid carrying immunostimulatory sequences (ISS) as well as a gene of interest (DNA vaccine) into professional antigen presenting cells (APC) induced transactivation of IL-12 mRNA, which resulted in antigen-specific Th1-biased immune responses against the encoded antigen. Th1-biased immune responses induced by DNA-based immunization were substantially upregulated by a codelivery of an ectopic IFN-gamma expression system, and this augmentation was mediated via action on professional antigen presenting cells to upregulate IL-12 production. Taken together, it appears likely that Th1-biased immune responses induced by DNA-based immunization are mediated via action on professional antigen-presenting cells to produce IL-12. Interestingly, the model provided strikingly resembles that previously described in infection with Listeria monocytogenes, an intracellular Gram-positive bacterium that induces strong Th1-biased immune responses. The result suggests that DNA-based immunization mimics certain aspects of natural infection with microbial organisms like attenuated vaccines, which in turn provides a rationale to the question of why DNA-based immunization so efficiently induces protective immunity against these microbial pathogens.
authors.affiliation: Department of Bacteriology, Yokohama City University School of Medeicine, Yokohama, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Asakura
authors.forename: L J
authors.initials: LJ
authors.lastname: Liu
authors.forename: N
authors.initials: N
authors.lastname: Shono
authors.forename: J
authors.initials: J
authors.lastname: Hinkula
authors.forename: A
authors.initials: A
authors.lastname: Kjerrström
authors.forename: I
authors.initials: I
authors.lastname: Aoki
authors.forename: K
authors.initials: K
authors.lastname: Okuda
authors.forename: B
authors.initials: B
authors.lastname: Wahren
authors.forename: J
authors.initials: J
authors.lastname: Fukushima
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology*; D001483:Base Sequence; D017931:DNA Primers / Q000235:genetics; D005260:Female; D019302:HIV Envelope Protein gp160 / Q000235:genetics / Q000276:immunology; D015497:HIV-1 / Q000235:genetics / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics; D018664:Interleukin-12 / Q000096:biosynthesis* / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology*; D014161:Transduction, Genetic; D014162:Transfection; D015854:Up-Regulation; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D016915:AIDS Vaccines; D017931:DNA Primers; D019302:HIV Envelope Protein gp160; D012333:RNA, Messenger; D019444:Vaccines, DNA; D018664:Interleukin-12; D007371:Interferon-gamma