The STING ligand cGAMP potentiates the efficacy of vaccine-induced CD8+ T cells

JCI Insight. 2019 Apr 4;4(7):e125107. doi: 10.1172/jci.insight.125107.

Abstract

Pathogen recognition receptor (PRR) agonists are currently being developed and tested as adjuvants in various formulations to optimize the immunogenicity and efficacy of vaccines. Using an original in vitro approach to prime naive precursors from unfractionated human peripheral blood mononuclear cells, we assessed the influence of cyclic guanosine monophosphate-adenosine monophosphate (cGAMP), a ligand for the stimulator of interferon genes (STING), on the induction of antigen-specific CD8+ T cells. We found that 2'3'-cGAMP and 3'3'-cGAMP were especially potent adjuvants in this system, driving the expansion and maturation of functionally replete antigen-specific CD8+ T cells via the induction of type I IFNs. The biological relevance of these findings was confirmed in vivo using two mouse models, in which 2'3'-cGAMP-adjuvanted vaccination elicited protective antitumor or antiviral CD8+ T cell responses. These results identify particular isoforms of cGAMP as effective adjuvants that may find utility in the development of novel immunotherapies and vaccines.

Keywords: T cells; Vaccines.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / administration & dosage*
  • Animals
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / metabolism
  • Cancer Vaccines / administration & dosage
  • Cancer Vaccines / immunology
  • Cell Line, Tumor / transplantation
  • Cells, Cultured
  • Disease Models, Animal
  • Female
  • HIV Infections / immunology
  • HIV Infections / prevention & control
  • HIV Infections / virology
  • HIV-1 / immunology
  • Humans
  • Immunogenicity, Vaccine
  • Interferon Type I / immunology
  • Interferon Type I / metabolism
  • Ligands
  • Membrane Proteins / agonists*
  • Mice
  • Nucleotides, Cyclic / administration & dosage
  • Nucleotides, Cyclic / immunology*
  • Primary Cell Culture
  • Thymoma / immunology
  • Thymoma / pathology
  • Thymoma / prevention & control
  • Thymus Neoplasms / immunology
  • Thymus Neoplasms / pathology
  • Thymus Neoplasms / prevention & control
  • Vaccination / methods*
  • Viral Vaccines / administration & dosage
  • Viral Vaccines / immunology

Substances

  • Adjuvants, Immunologic
  • Cancer Vaccines
  • Interferon Type I
  • Ligands
  • Membrane Proteins
  • Nucleotides, Cyclic
  • STING1 protein, human
  • Viral Vaccines
  • cyclic guanosine monophosphate-adenosine monophosphate