Cyclic Guanosine Monophosphate-Adenosine Monophosphate (cGAMP) as Vaccine Adjuvant

cGAMP, which can enhance the efficacy of vaccine-induced CD8+ T cells, is currently being developed as adjuvants in various formulations to optimize the efficacy and immunogenicity of vaccines. 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 cGAMP.

Cyclic Guanosine Monophosphate-Adenosine Monophosphate (cGAMP)

Common STING ligands include cyclic dinucleotides (CDNs), such as cGAMP, c-di-GMP, and c-di-AMP, which play important roles in the field of immunology and microbiology. They function as second messengers and participate in the signal transduction of cytosolic DNA immune responses, enhancing Ig production and T-cell responses by binding to STING.

In mammalian cells, cGAMP is synthesized from cytosolic DNA by cGAMP synthase (cGAS). cGAMP then binds to stimulator of interferon genes (STING) to induce interferon (IFN) regulatory factor 3-dependent and nuclear factor-kappa B-dependent production of type I IFN. As a naturally metabolizable molecule in the human body, cGAMP is rapidly hydrolyzed by phosphodiesterase when it is outside the plasma membrane, which ensures that its adjuvant activity is transient, effectively avoiding unwanted systemic inflammation. In addition, since cGAMP is a negatively charged small molecule hydrophilic molecule, it is highly unlikely that antibodies against such small molecules themselves are induced.

2' 3'-cyclic guanosine monophosphate-adenosine monophosphate (2' 3'-cGAMP) and 3' 3'-cyclic guanosine monophosphate-adenosine monophosphate (3' 3'-cGAMP) are particularly effective adjuvants in this system by inducing type I IFN to drive the expansion and maturation of sufficient antigen-specific CD8+ T cells. These specific isoforms of cGAMP act as effective adjuvants for the development of novel immunotherapies and vaccines.

Skeletal formula of cyclic guanosine monophosphate.

Fig.1 Skeletal formula of cyclic guanosine monophosphate.

cGAMP as Cancer Vaccine Adjuvant

cGAMP is an effective adjuvant for inducing de novo CD8+ T cell responses and may enable new immunotherapeutic and prophylactic methods to treat a variety of infectious diseases and cancers. cGAMP is as effective as polyI:C in inducing IgA production and antigen-specific T cell responses. Adjuvant activity is not type I IFN dependent, but rather depends on STING recognition of cGAMP. It may be particularly suitable for the primary effector CD8+ T cells against new tumor antigens identified in cancer patients. In addition, the ability of cGAMP to trigger humoral immune responses in parallel, including secretion of mucosal surface IgA, may have further advantages in the production of certain viral infections such as HIV-1. The isoform of cGAMP acts as an effective adjuvant in vitro and in vivo, enhancing the induction of a functional antigen-specific CD8+ T cell response in humans and the induction of a protective antigen-specific CD8+ T cell response in mice.

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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