ODN 1018 VacciGrade™ - TLR9-based Adjuvant

CpG ODNs

Synthetic oligodeoxynucleotides containing unmethylated CpG motifs (CpG ODNs) have been extensively studied as adjuvants [1]. These CpG motifs are present at a 20-fold greater frequency in bacterial DNA compared to mammalian DNA [2]. CpG ODNs are recognized by the Toll-like receptor 9 (TLR9), which is expressed on human B cells and plasmacytoid dendritic cells (pDCs), thereby inducing Th1-dominated immune responses [3]. Pre-clinical studies, conducted in rodents and non-human primates, as well as human clinical trials, have demonstrated that CpG ODNs can significantly improve vaccine-specific antibody responses [1]. Three types of stimulatory CpG ODNs have been identified, types A, B, and C, which differ in their immune-stimulatory activities [4-5].

1018 ISS

1018 immunostimulatory sequence (ISS) is a type B CpG ODN with the sequence 5′-TGACTGTGAACGTTCGAGATGA-3′. It mimics bacterial single-stranded (ss) DNA to activate innate immunity through binding to TLR9. The first CpG motif (underlined) is a sequence active on mouse TLR9, whereas the second CpG motif (bold) is active on human and non-human primate TLR9 [6]. Type B CpG ODNs contain a full phosphorothioate backbone with one or more CpG dinucleotides and were described to strongly activate the Th1 cell and B cell populations [4,6]. CpG motifs present in the 1018 sequence stimulate the innate immune system, which results in efficacious immunological effects, such as the production of IL-12, IL-18, and IFN-γ from macrophages and natural killer (NK) cells, promoting Th1 responses, and its involvement in antibody production and B cell proliferation [7]. The GMP-produced CpG 1018® produced by Dynavax Technologies is currently the only FDA-approved CpG adjuvant for human vaccine use. It is a component of several approved vaccines, including the licensed hepatitis B virus vaccine HEPLISAV-B® [8].

Note: CpG 1018® is a registered trademark of Dynavax Technologies and is used for comparative purposes only. ODN 1018 VacciGrade™​ is not made by, affiliated with, sponsored by, or endorsed by Dynavax Technologies.

References:

1. Steinhagen F. et al., 2011. TLR-based immune adjuvants. Vaccine 29(17):3341-55.
2. Hemmi H. et al., 2000. A Toll-like receptor recognizes bacterial DNA. Nature 408:740-5.
3. Coffman RL. et al., 2010. Vaccine adjuvants: Putting innate immunity to work. Immunity 33(4):492-503.
4. Krug A. et al., 2001. Identification of CpG oligonucleotide sequences with high induction of IFN-alpha/beta in plasmacytoid dendritic cells. Eur J Immunol, 31(7): 2154-63.
5. Marshall JD. et al., 2005. Superior activity of the type C class of ISS in vitro and in vivo across multiple species. DNA Cell Biol. 24(2):63-72.
6. Campbell JD, 2017. Development of the CpG Adjuvant 1018: A Case Study. Methods Mol Biol. 1494:15-27.
7. Eng NF, et al., 2013. The potential of 1018 ISS adjuvant in hepatitis B vaccines: HEPLISAV™ review. Hum Vaccin Immunother.(8):1661-72.
8. Strohmeier S, et al., 2022. A CpG 1018 adjuvanted neuraminidase vaccine provides robust protection from influenza virus challenge in mice. NPJ Vaccines. 2022 Jul 22;7(1):81.