Cyclic GMP-AMP displays mucosal adjuvant activity in mice

PLoS One. 2014 Oct 8;9(10):e110150. doi: 10.1371/journal.pone.0110150. eCollection 2014.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptive Immunity / drug effects
  • Adjuvants, Immunologic / chemistry
  • Adjuvants, Immunologic / pharmacology*
  • Animals
  • Dendritic Cells / drug effects
  • Dendritic Cells / immunology
  • Female
  • Humans
  • Immunity, Humoral / drug effects
  • Immunoglobulin G / metabolism
  • Isomerism
  • Mice
  • Mice, Inbred C57BL
  • Mucous Membrane / drug effects
  • Mucous Membrane / immunology
  • Nucleotides, Cyclic / chemistry
  • Nucleotides, Cyclic / pharmacology*
  • Ovalbumin / immunology
  • Th1 Cells / drug effects
  • Th1 Cells / immunology
  • Th2 Cells / drug effects
  • Th2 Cells / immunology
  • Vaccination

Substances

  • Adjuvants, Immunologic
  • Immunoglobulin G
  • Nucleotides, Cyclic
  • cyclic guanosine monophosphate-adenosine monophosphate
  • Ovalbumin