title: DNA vaccines: a simple DNA sensing matter?
abstract: Since the introduction of DNA vaccines two decades ago, this attractive strategy has been hampered by its low immunogenicity in humans. Studies conducted to improve the immunogenicity of DNA vaccines have shown that understanding the mechanism of action of DNA vaccines might be the key to successfully improving their immunogenicity. Our current understanding is that DNA vaccines induce innate and adaptive immune responses in two ways: (1) encoded protein (or polypeptide) antigen(s) by the DNA plasmid can be expressed in stromal cells (i.e., muscle cells) as well as DCs, where these antigens are processed and presented to naïve CD4 or CD8 T cells either by direct or cross presentation, respectively; and (2) the transfected DNA plasmid itself may bind to an un-identified cytosolic DNA sensor and activate the TBK1-STING pathway and the production of type I interferons (IFNs) which function as an adjuvant. Recent studies investigating double-stranded cytosolic DNA sensor(s) have highlighted new mechanisms in which cytosolic DNA may release secondary metabolites, which are in turn recognized by a novel DNA sensing machinery. Here, we discuss these new metabolites and the possibilities of translating this knowledge into improved immunogenicity for DNA vaccines.
authors.affiliation: Laboratory of Malaria Immunology; WPI Immunology Frontier Research Center (IFReC); Osaka University; Osaka, Japan.
authors.forename: Cevayir
authors.initials: C
authors.lastname: Coban
authors.affiliation: Laboratory of Adjuvant Innovation; National Institute of Biomedical Innovation; Osaka, Japan; Laboratory of Vaccine Science; IFReC; Osaka University; Osaka, Japan.
authors.forename: Kouji
authors.initials: K
authors.lastname: Kobiyama
authors.affiliation: Laboratory of Adjuvant Innovation; National Institute of Biomedical Innovation; Osaka, Japan.
authors.forename: Nao
authors.initials: N
authors.lastname: Jounai
authors.affiliation: Laboratory of Adjuvant Innovation; National Institute of Biomedical Innovation; Osaka, Japan.
authors.forename: Miyuki
authors.initials: M
authors.lastname: Tozuka
authors.affiliation: Laboratory of Adjuvant Innovation; National Institute of Biomedical Innovation; Osaka, Japan; Laboratory of Vaccine Science; IFReC; Osaka University; Osaka, Japan.
authors.forename: Ken J
authors.initials: KJ
authors.lastname: Ishii
mesh_terms: D056704:Adaptive Immunity; D000276:Adjuvants, Immunologic / Q000378:metabolism; D000818:Animals; D004247:DNA / Q000378:metabolism; D006801:Humans; D007113:Immunity, Innate; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000276:immunology; D019444:Vaccines, DNA / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D011994:Recombinant Proteins; D019444:Vaccines, DNA; D004247:DNA
keywords: DNA vaccine; STING; TBK1; adjuvant; type I interferon
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