CpG

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Vaccine Adjuvant - Creative Biolabs

CpG

CpG is a higher frequency of unmethylated deoxycytidyl-deoxyguanosine dinucleotides in bacterial genome. Small oligodeoxynucleotides (ODN) with unmethylated CpG (CpG ODN) are able to perfectly mimic the immunostimulatory activity of bDNA. CpG ODNs bind to and trigger cells that express Toll-like receptor 9 (TLR9), booting an innate immune response that supports the subsequent development of adaptive immunity. Researches demonstrate that TLR9 agonists improve antigen presentation and the induction of vaccine-specific cellular and humoral responses. More than 100 clinical trials utilizing CpG ODNs have been conducted that evaluated their utility in preventing or treating allergy, infectious diseases, and cancer.

The Structure of CpG ODNs

Based on structure and biological function on human peripheral blood mononuclear cells (PBMCs), in particular, B cells and plasmacytoid dendritic cells (pDCs), the CpG-containing sequences have been divided into three general classes. These three classes are Class A (Type D), Class B (Type K) and Class C. CpG-B class molecules are the most frequently used in clinical vaccine studies. Structure and function are closely related for CpG ODNs. Indeed, the higher order structure of the molecule determines whether the CpG ODN localizes intracellularly to early or late endosomes, compartments associated with different signaling pathways. Multimeric CpG-A ODNs predominantly localize to early endosomes, where in plasmacytoid dendritic cells they result in strong induction of IFN-α. Monomeric CpG-B ODNs concentrate in the late endosomal compartment and can promote cellular maturation of both plasmacytoid dendritic cells and B cells. CpG-C ODNs localize to both compartments, inducing IFN-α production and cellular maturation. Additional structural modifications that influence the biological effects of CpG-containing sequences include linking two or more short phosphorothioate-backbone CpG-ODNs by non-nucleoside chemical linkers to produce linear chimeric immunomodulatory compounds and/or formulation of CpG-containing nanoparticle compounds.

Immunostimulation by CpG ODNs

Like TLR-4 agonists, CpG-ODNs have been extensively tested in the clinic and also promote Th1 responses. CpG-ODN signal through TLR-9 on plasmacytoid dendritic cells to induce potent IFN-α production and, indirectly through natural killer cells, IFN-γ secretion. In addition, CpG-ODNs also directly stimulate maturation in TLR9-expressing B cells. As adjuvants for vaccines, CpG-ODNs thus activate professional antigen-presenting cells, thereby enhancing the induction of antibody responses to co-administered protein antigens. One of the CpG-ODNs is currently in advanced-stage clinical development as an adjuvant for hepatitis B surface antigen (HBsAg) immunization against hepatitis B virus (HBV). CpG ODNs as adjuvant for use in vaccine development can improve the function of professional antigen-presenting cells and boost the generation of humoral and cellular vaccine-specific immune responses. The adjuvant properties of CpG ODNs are observed when administered either systemically or mucosally and persist in immunocompromised hosts. Preclinical studies indicate that CpG ODNs improve the activity of vaccines targeting infectious diseases and cancer. A mount of researches confirm that CpG ODNs have a good safety profile and would increase the immunogenicity of coadministered vaccines. Application as adjuvant to vaccine production, CpG ODN has great potential to better service to the broad market.

Effect of CpG ODNs

Fig. 2 Effect of CpG ODNs

Creative Biolabs is a leader in the field of vaccine adjuvant development and has focused on the CpG-ODNs adjuvants for many years. We have experts who are able to help you with the development of the CpG-ODNs for use in vaccines. If you are interested in our services, please contact us for more details.

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Reference

  1. Christian Bode. (2011). “CpG DNA as a vaccine adjuvant” Expert Rev Vaccines, 10(4): 499–511.

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