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CDG |
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Vaxjo ID |
210 |
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Vaccine Adjuvant Name |
CDG |
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Alternative Names |
c-di-GMP |
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Adjuvant VO ID |
VO_0005557
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Description |
It is a bacterial second messenger and a promising mucosal adjuvant candidate that activates balanced Th1/Th2/Th17 responses. It activates stimulator of IFN genes (STING)-dependent IFN-I production in vitro and STING-dependent, IFN-I-independent TNF-¦Á production in vivo and in vitro. |
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Stage of Development |
Research |
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Components |
The bacterial second messenger (3'-5')-cyclic-di-guanosine-monophosphate (CDG) is a promising mucosal adjuvant candidate that activates balanced Th1/Th2/Th17 responses. |
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Dosage |
The paper states patients were immunized at D0, 8, 15, 22, 28, 52, and 74 post-reinfusion, but the specific dosage of IMP321 is not detailed in the abstract. |
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Function |
In this study, we show that STING-deficient (Tmem173⁻/⁻) mice fail to produce antigen-specific antibodies and Th1/Th2/Th17 cytokines after CDG/Ag immunization, with no induction of TNF-α, IL-1β, IL-6, IL-12, or MCP-1 upon intranasal CDG administration. Notably, IFNAR⁻/⁻ mice retain normal cytokine and antibody responses, indicating CDG triggers STING-dependent but IFN-I-independent TNF-α production both in vivo and in vitro. Using TNFR1⁻/⁻ mice, we confirm that TNF-α signaling is essential for CDG-induced antigen-specific antibody and Th1/Th2 cytokine responses. This mechanism differs from STING-mediated DNA adjuvant activity, which requires IFN-I but not TNF-α. Additionally, CDG activates STING-dependent, IRF3-independent NF-κB signaling. Our results reveal a critical STING–NF-κB–TNF-α pathway underlying CDG’s mucosal adjuvant activity, independent of IFN-I. |
| References |
Blaauboer et al., 2014: Blaauboer SM, Gabrielle VD, Jin L. MPYS/STING-mediated TNF-α, not type I IFN, is essential for the mucosal adjuvant activity of (3'-5')-cyclic-di-guanosine-monophosphate in vivo. Journal of immunology (Baltimore, Md. : 1950). 2014; 192(1); 492-502. [PubMed: 24307739].
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