CpG-2722 and STING Agonist Combination for Using as Vaccine Adjuvant
CpG-2722 和 STING 激動劑組合用作 疫苗佐劑
Combination of CpG-2722 and STING agonist generates an enhanced adjuvant activity for intranasal and intramuscular injected vaccines
CpG-2722 和 STING 激動劑的組合產生增強的鼻內和肌內註射疫苗的佐劑活性
Targeted indication
Vaccine adjuvant
Status
Pre-clinical studies
Key features
- CpG-2722 has good immunostimulatory in different species including human, mouse, fish, chicken and duck.
- CpG-2722 has good activity in induction of inflammatory cytokines, IL-12 and interferons.
- Vaccine adjuvanted with CpG-2722 orSTING agonist alone is able to induce immune responses. The adjuvant activity is increased when both are formulated together.
- The CpG-2722 and STING agonist combination can be used as adjuvant for intranasal and intramuscular administrated vaccines.
Market
Vaccines are a powerful tool for control of spreading of microbial infections and epidemic diseases.
The efficiency of a vaccine usually rely on an effective adjuvant to boost immune responses.
Since the discovery of aluminum salts as a vaccine adjuvant in the 1920s, fewer than 15 different adjuvants are used in vaccines for humans.
Therefore, novel and effective adjuvants for development of effective vaccines remaining have their market.
MODE OF ACTION
Cooperative adjuvant effect of the CpG-2722 and STING agonist combination.
Combinations of CpG-2722 with various STING agonists as vaccine adjuvant increase germinal center (GC) B cell response and elicit humoral immune responses in immunized mice. CpG-2722 induced both antigen-dependent and -independent T helper (Th)1 and Th17 immune responses. STING agonist induced antigen-dependent and -independent Th2 immune response. The combination of CpG-2722 and STING agonist generated a distinct Th response profile. The increased GC B cell response and reshaped Th response are the molecular bases for the cooperative adjuvant effect of the CpG-2722 and STING agonist combinations.
EXPERIMENTAL RESULTS
In splenocytes and peripheral blood mononuclear cells, CpG-2722 induced a Th1 polarized cytokine production. In contrast STING agonist activated Th2 polarized cytokine production. Combination of these two agents resulted in a distinct cytokine producing profile to increase the adjuvant activity.
Mice were intranasally and intramuscularly injected with CpG-2722 and STING agonist alone or combination adjuvanted SARS-CoV-2 receptor binding domain (RBD) protein vaccine. The vaccine adjuvanted with combination of CpG-2722 and STING agonist generated the highest humoral responses against the SARS-CoV-2.
CpG-ODN has been approved for use as adjuvant in human vaccines. CpG-2722, basically like other CpG-ODNs, is a synthetic phosphothiolated deoxyoligonucleotides. Therefore, it is expected that CpG-2722 is able to have the same biosafety profile as other CpG-ODNs. STING agonists have been investigated in different stages of clinical trials for cancer therapy. Therefore, it is likely to have good safety profile in human.
However, because the CpG-2722 has different nucleotide sequences and different immunostimulatory activity from other CpG-ODNs. Moreover, the combination of CpG-2722 and STING agonist for using as vaccine adjuvant has not yet been investigated in humans, it is still required to follow the relevant government regulations to test the properties of CpG-2722 and STING agonist combination and approved by the government agency before conducting clinical trials.
Both CpG-2722 and STING agonists have good water solubility. In this study, the vaccines were administrated by intranasal delivery and intramuscular injection.
INTELLECTUAL PROPERTY
SELECTED PUBLICATIONS
Yang et al. Manuscript in submission.
Chuang et al. Vaccines (Basel). 2020;8(4):639.
Yeh et al. Sci Rep. 2017;7(1):17297.
BUSINESS OPPORTUNITY
License and/or Collaboration and Sponsored Research
CONTACT
service@biip-dcc.org