c-di-AMP VacciGrade™

Cyclic diadenylate monophosphate - STING agonist

Cyclic diadenylate monophosphate (c-di-AMP) is a cyclic dinucleotide (CDN) produced by bacteria in which it functions as an essential second messenger [1]. It coordinates bacterial growth, cell wall stability, and responses to stress and plays a crucial role in the establishment of bacterial infection.

CDNs are a relatively new class of adjuvants that have been shown to increase vaccine potency [2]. CDNs activate innate immunity by directly binding the endoplasmic reticulum-resident receptor STING (stimulator of interferon genes), activating a signaling pathway that induces the expression of interferon-β (IFN-β) and also nuclear factor-κB (NF-κB) dependent inflammatory cytokines [3, 4].

Recent studies have also demonstrated that c-di-AMP exerts strong adjuvant activities when delivered by the mucosal route [5, 6].

c-di-AMP VacciGrade™ is a preclinical grade preparation of the cyclic dinucleotide c-di-AMP.

c-di-AMP VacciGrade™ is for research use only, not for use in humans.

References:

1. Witte CE. et al., 2013. Cyclic di-AMP is critical for Listeria monocytogenes growth, cell wall homeostasis, and establishment of infection. MBio. 4(3):e00282-13.
2. Dubensky TW. et al., 2013. Rationale, progress and development of vaccines utilizing STING-activating cyclic dinucleotide adjuvants. Therapeutic Advances in Vaccines 1(4): 131-143.
3. Jin L. et al., 2011. MPYS is required for IFN response factor 3 activation and type I IFN production in the response of cultured phagocytes to bacterial second messengers cyclic-di-AMP and cyclic-di-GMP. J Immunol. 187(5):2595-601.
4. Burdette DL. et al., 2011. STING is a direct innate immune sensor of cyclic di-GMP. Nature. 478(7370):515-8.
5. Ebensen T. et al., 2011. Bis-(3',5')-cyclic dimeric adenosine monophosphate: strong Th1/Th2/Th17 promoting mucosal adjuvant.Vaccine. 29(32):5210-20.
6. Škrnjug I. et al., 2014. The mucosal adjuvant cyclic di-AMP exerts immune stimulatory effects on dendritic cells and macrophages. PLoS One. 9(4):e95728.

Figures

THP1-Dual™ cells were stimulated for 24 hours with the STING ligands as shown (all at 10 μg/ml). IRF induction was determined by measuring the relative light units (RLUs) in a luminometer using QUANTI‑Luc™, a Lucia luciferase detection reagent.

THP1-Dual™ cells were stimulated for 24 hours with the STING ligands as shown (all at 10 μg/ml). NF‑kB induction was determined using QUANTI‑Blue™, a SEAP detection reagent, and by reading the optical density (OD) at 655 nm. Non-induced cells (NI) have been included as a negative control.

Specifications

Description: STING agonist

Synonym: Cyclic di-adenylate monophosphate, c-di-AMP sodium salt

CAS number: 54447-84-6

Formula: C₂₀H₂₂N₁₀O₁₂P₂ .2Na

Molecular weight: 702.38

Purity: ≥ 95% by LC/MS

Solubility: 50 mg/ml in water

Quality: Sterile

Endotoxin Level: Lower than 0.005 EU/μg

Biological activity: Assessed by measuring induction of the interferon pathway in THP1-Blue™ ISG cells

Contents

• 1 mg of lyophilized c-di-AMP VacciGrade™
• 10 ml sterile endotoxin-free physiological water (NaCl 0.9%)

c-di-AMP VacciGrade™ is shipped at room temperature

c-di-AMP VacciGrade™  should be stored at -20°C.

Details

c-di-AMP VacciGrade™ is a preclinical grade preparation of the cyclic dinucleotide c-di-AMP.

It is prepared under strict aseptic conditions and is tested for the presence of endotoxins.

c-di-AMP VacciGrade™ is guaranteed sterile.

Its endotoxin level is lower than 0.005 EU/μg.