Cyclic Dimeric Inosine Monophosphate (c-di-IMP) as Vaccine Adjuvant

When administered by mucosal or systemic routes, c-di-IMP exhibits potent activity as an adjuvant. It has comparable capacities to c-di-GMP in promoting the activation and maturation of DC and enhancing stimulatory capacities on macrophages. Creative Biolabs is a leader in the field of vaccine development and the extensive experience and expertise of our scientists enable us to provide development services related to innate immune stimulators, particularly the adjuvant development of c-di-IMP.

Cyclic Dimeric Inosine Monophosphate (c-di-IMP)

c-di-IMP is a second messenger synthesized by bacteria from two GTP precursors which are hydrolyzed and circularized by a 5-3 monophosphate bond and was originally described as playing an important role in bacterial cell-cell communication. Naturally occurring c-di-IMP is a required but poorly understood bacterial signaling molecule regulating the various functions involved in the quiescent state transitions found in biofilms. It is a small signaling molecule that also exerts effector functions on eukaryotic cells, probably by acting as a danger signal. When administered by mucosal or systemic routes, c-di-IMP exhibits potent activity as an adjuvant. c-di-IMP promotes efficient activation and maturation of DCs in vitro, as evidenced by up-regulated expression of MHC class I and class II, costimulatory (CD80, CD86) and adhesion (CD40, CD54) molecules.

Fig.1 Chemical structure of c-di-IMP.

c-di-IMP as Mucosal Adjuvant

Structurally related to the bacterial second messengers c-di-GMP and c-di-AMP, c-di-IMP also has adjuvant properties when co-administered with antigens in vitro and by mucosal routes in vivo. c-di-IMP exhibits comparable capacities to c-di-GMP in promoting the activation and maturation of DC and enhancing stimulatory capacities on macrophages. Moreover, regarding the cellular responses, spleen cells from mice immunized with c-di-IMP showed a higher proliferation than those vaccinated with c-di-GMP. c-di-IMP shows strong immunomodulatory properties that can be used to optimize the response elicited after vaccination. c-di-IMP has become a promising candidate adjuvant for vaccine development.

The incorporation of c-di-IMP into the formulation leads to the initiation of a mixed TH1/TH2/TH17 response. Co-administration of antigens with c-di-IMP by i.n. route results in strong stimulation of systemic and local levels of humoral and cellular immune responses. More specifically, high titres of -Gal-specific IgG were detected in sera of vaccinated mice, even after a single boost. In summary, many studies have shown that c-di-IMP is a promising candidate adjuvant for the development of mucosal vaccines against pathogens that require TH1, TH2 or TH17 responses for efficient clearance.

Creative Biolabs is specialized in assisting clients with every stage of the vaccine development services, including adjuvant optimization. As an innovative and truly premier drug discovery and development research partner, Creative Biolabs is committed to providing the best quality services and high level of specialized support.

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