V155M |
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Vaxjo ID |
237 |
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Vaccine Adjuvant Name |
V155M |
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Adjuvant VO ID |
VO_0005724
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Description |
A gain-of-function mutant of STING that activates type I interferon and NF-κB pathways. Encoded via mRNA and delivered using lipid nanoparticles (LNPs) as a genetic adjuvant |
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Stage of Development |
Research |
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Host Species for Testing |
3 |
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Components |
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 |
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Structure |
Encoded as modified mRNA, formulated into LNPs; the V155M point mutation enhances STING activity by localizing it to specific intracellular compartments |
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Appearance |
Formulated in LNPs; 80–100 nm particles in diameter |
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Storage |
Stored frozen; LNP formulations stable when frozen |
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Preparation |
mRNA synthesized with pseudouridine, encapsulated into LNPs using ethanol-lipid mixing, followed by filtration and diafiltration |
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Dosage |
Typically 10 µg mRNA per mouse, administered intramuscularly on days 0 and 14 |
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Function |
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. |
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Safety |
Well tolerated in mice; cytokine response is transient; no prolonged inflammation observed; adjuvant activity dependent on CD8⺠T cells |
| References |
Tse et al., 2021: Tse SW, McKinney K, Walker W, Nguyen M, Iacovelli J, Small C, Hopson K, Zaks T, Huang E. mRNA-encoded, constitutively active STING(V155M) is a potent genetic adjuvant of antigen-specific CD8(+) TÂ cell response. Molecular therapy : the journal of the American Society of Gene Therapy. 2021; 29(7); 2227-2238. [PubMed: 33677092].
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