mRNA-encoded, constitutively active STINGV155M is a potent genetic adjuvant of antigen-specific CD8+ T cell response

Mol Ther. 2021 Jul 7;29(7):2227-2238. doi: 10.1016/j.ymthe.2021.03.002. Epub 2021 Mar 5.


mRNA vaccines induce potent immune responses in preclinical models and clinical studies. Adjuvants are used to stimulate specific components of the immune system to increase immunogenicity of vaccines. We utilized a constitutively active mutation (V155M) of the stimulator of interferon (IFN) genes (STING), which had been described in a patient with STING-associated vasculopathy with onset in infancy (SAVI), to act as a genetic adjuvant for use with our lipid nanoparticle (LNP)-encapsulated mRNA vaccines. mRNA-encoded constitutively active STINGV155M was most effective at maximizing CD8+ T cell responses at an antigen/adjuvant mass ratio of 5:1. STINGV155M appears to enhance development of antigen-specific T cells by activating type I IFN responses via the nuclear factor κB (NF-κB) and IFN-stimulated response element (ISRE) pathways. mRNA-encoded STINGV155M increased the efficacy of mRNA vaccines encoding the E6 and E7 oncoproteins of human papillomavirus (HPV), leading to reduced HPV+ TC-1 tumor growth and prolonged survival in vaccinated mice. This proof-of-concept study demonstrated the utility of an mRNA-encoded genetic adjuvant.

Keywords: CD8; DAMP; PRR; STING; T cells; adjuvant; damage-associated molecular patterns; mRNA vaccine; pattern-recognition receptors; type-1 interferons; vaccine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic
  • Animals
  • Apoptosis
  • CD8-Positive T-Lymphocytes / immunology*
  • Cancer Vaccines / administration & dosage*
  • Cancer Vaccines / genetics
  • Cancer Vaccines / immunology
  • Cell Proliferation
  • Dendritic Cells / immunology
  • Disease Models, Animal
  • Female
  • Humans
  • Liposomes / chemistry
  • Lung Neoplasms / immunology
  • Lung Neoplasms / pathology
  • Lung Neoplasms / therapy*
  • Membrane Proteins / genetics
  • Membrane Proteins / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Nanoparticles / chemistry
  • Papillomavirus E7 Proteins / immunology*
  • RNA, Messenger / genetics
  • RNA, Messenger / immunology*
  • T-Lymphocytes, Cytotoxic / immunology
  • Tumor Cells, Cultured
  • mRNA Vaccines / administration & dosage
  • mRNA Vaccines / genetics
  • mRNA Vaccines / immunology*


  • Adjuvants, Immunologic
  • Cancer Vaccines
  • Lipid Nanoparticles
  • Liposomes
  • Membrane Proteins
  • Papillomavirus E7 Proteins
  • RNA, Messenger
  • Sting1 protein, mouse
  • mRNA Vaccines