Cyclic Diguanylate Monophosphate (c-di-GMP) as Vaccine Adjuvant
Cyclic dinucleotides are unique nucleic acids functioning as conserved signaling molecules in bacteria and can induce a STING-dependent type I IFN response, which have shown promise as novel vaccine adjuvants. 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-GMP.
Cyclic Diguanylate Monophosphate (c-di-GMP)
Although nucleotides are key signaling molecules in all life, cyclic dinucleotides appear to be produced only by bacteria and archaea. Cyclic diguanylate (c-di-GMP) is a bacterial nucleotide second messenger that regulates many processes including biofilm formation, motility, and virulence gene expression. Since they are unique to microorganisms, cyclic dinucleotides serve as appropriate targets for immune recognition and can be used as immunomodulators and adjuvants. c-di-GMP is a potent activator of humoral and Th1-like immune responses that enhances immune responses in immunization against bacterial pathogens.
Fig.1 Chemical structures of c-di-GMP and its sulfur analogues (c-di-GMP-S1 and -S2). (Chen W, et al. 2010)
c-di-GMP as a Systemic Adjuvant
The fact that c-di-GMP is able to stimulate and modulate host innate immune responses suggests that c-di-GMP (and its analogs) may be a potential vaccine adjuvant. The presence of IgG1 and IgG2a subclasses in serum and cytokine profiles in re-stimulated spleen cells suggest that vaccines with c-di-GMP adjuvant induce balanced Th1 and Th2 immune responses, making c-di-GMP a good adjuvant candidate. What's more, antigens adjuvanted with c-di-GMP appears to trigger higher levels of specific antibodies and better protective immunity than antigens adjuvanted with alum.
c-di-GMP as a Mucosal Adjuvant
c-di-GMP has the potential to be a mucosal adjuvant because human mucosal surfaces (such as the respiratory tract, genitourinary tract and gastrointestinal tract) are the portals of entry and the site of disease caused by microbial pathogens. Chen W et al. demonstrated that mucosal immune responses induced with c-di-GMP-adjuvanted vaccines did translate into protective immunity against bacterial infections. They showed that mice i.n. immunized with c-di-GMP-adjuvant pneumococcal surface adhesin A (PsaA) induced specific IgA in both local bronchoalveolar space and distal mucosal sites (feces) as well as serum IgG1 and IgG2a responses.
Fig.2 Antitumor mechanisms of STING ligand c-di-GMP. (Gravekamp C and Chandra D. 2015)
A large amount of research is still needed before c-di-GMP could be included as a vaccine adjuvant in human clinical trials, but initial research has highlighted the enormous potential of c-di-GMP as a vaccine adjuvant. 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. Please contact us for more information.
References
- Chen W, et al. The potential of 3',5'-cyclic diguanylic acid (c-di-GMP) as an effective vaccine adjuvant. Vaccine. 2010, 28(18): 3080-5.
- Gravekamp C and Chandra D. Targeting STING pathways for the treatment of cancer. Oncoimmunology. 2015, 4(12): e988463.
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