MRNA-encoded, constitutively active STING^V155M is a potent genetic adjuvant of antigen-specific CD8⁺ T cell response.

ABSTRACT: 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 STING^V155M was most effective at maximizing CD8⁺ T cell responses at an antigen/adjuvant mass ratio of 5:1. STING^V155M 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 STING^V155M 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.

SUBMITTER: Tse SW 

PROVIDER: S-EPMC8261085 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature