title: Cyclic GMP-AMP displays mucosal adjuvant activity in mice.
abstract: The recently discovered mammalian enzyme cyclic GMP-AMP synthase produces cyclic GMP-AMP (cGAMP) after being activated by pathogen-derived cytosolic double stranded DNA. The product can stimulate STING-dependent interferon type I signaling. Here, we explore the efficacy of cGAMP as a mucosal adjuvant in mice. We show that cGAMP can enhance the adaptive immune response to the model antigen ovalbumin. It promotes antigen specific IgG and a balanced Th1/Th2 lymphocyte response in immunized mice. A characteristic of the cGAMP-induced immune response is the slightly reduced induction of interleukin-17 as a hallmark of Th17 activity--a distinct feature that is not observed with other cyclic di-nucleotide adjuvants. We further characterize the innate immune stimulation activity in vitro on murine bone marrow-derived dendritic cells and human dendritic cells. The observed results suggest the consideration of cGAMP as a candidate mucosal adjuvant for human vaccines.
authors.affiliation: Department of Vaccinology and Applied Microbiology, Helmholtz Centre for Infection Research, Braunschweig, Germany.
authors.forename: Ivana
authors.initials: I
authors.lastname: Škrnjug
authors.affiliation: Department of Vaccinology and Applied Microbiology, Helmholtz Centre for Infection Research, Braunschweig, Germany.
authors.forename: Carlos Alberto
authors.initials: CA
authors.lastname: Guzmán
authors.affiliation: Department of Vaccinology and Applied Microbiology, Helmholtz Centre for Infection Research, Braunschweig, Germany.
authors.forename: Christine
authors.initials: C
authors.lastname: Rueckert
authors.affiliation: Department of Vaccinology and Applied Microbiology, Helmholtz Centre for Infection Research, Braunschweig, Germany.
authors.forename: Christine
authors.initials: C
authors.lastname: Ruecker
mesh_terms: D056704:Adaptive Immunity / Q000187:drug effects; D000276:Adjuvants, Immunologic / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology; D005260:Female; D006801:Humans; D056724:Immunity, Humoral / Q000187:drug effects; D007074:Immunoglobulin G / Q000378:metabolism; D007536:Isomerism; D051379:Mice; D008810:Mice, Inbred C57BL; D009092:Mucous Membrane / Q000187:drug effects / Q000276:immunology; D009712:Nucleotides, Cyclic / Q000737:chemistry / Q000494:pharmacology*; D010047:Ovalbumin / Q000276:immunology; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology; D014611:Vaccination
chemical_list: D000276:Adjuvants, Immunologic; D007074:Immunoglobulin G; D009712:Nucleotides, Cyclic; C584311:cyclic guanosine monophosphate-adenosine monophosphate; D010047:Ovalbumin