Japan Digestive Disease Week 2021
International Session (Workshop)1 (JSGE, JSH)
November 4, 15:00–17:00, Room 11 (Portopia Hotel South Wing Topaz)
IS-W1-7_G
SA-5, A novel oral agonist of Toll-like Receptor (TLR) 7, induces HBs antigen specific immune reaction in chronic HBV infection model mice
- 1
- Department of Laboratory Medicine, Gifu University Graduate School of Medicine
- 2
- Department of Joint Research Laboratory of Clinical Medicine, Fujita Health University
- 3
- Department of Integrated Health Sciences, Nagoya University Graduate School of Medicine
Aims
A persistent hepatitis B virus (HBV) infection is characterized by a weak immune response to HBV. TLR 7 agonist has been reported to induce an innate cytokine response that suppresses HBV replication and to shape the adaptive immune response in chimpanzees. In the present study, we investigate the effect of SA-5 on immune activation against HBs antigen (Ag) using HBsAg transgenic mice lineage 107-5D.
Method
SA-5 was orally administered once a week for 4 weeks at 3 mg/kg. Serum sample was obtained twice a week. Liver tissue and splenocytes were obtained 7 days after the last SA-5 administration. Afterwards Immunohistochemistry and Enzyme-Linked ImmunoSpot (ELISPOT) assay followed.
Result
Serum level of alanine aminotransferase (ALT) increased in the following day of SA-5 administration but returned to the baseline 7days after. The positive cells of HBsAg immunohistochemistry significantly deceased in the SA-5 group compared with the control group. The SA5-treated mice mounted stronger cellular responses against HBsAg in ELISPOT assay and the spot number was negatively correlated with HBsAg immunohistochemistry positive cells.
Conclusion
SA5 may overcome immune tolerance in patients with chronic HBV infection.
A persistent hepatitis B virus (HBV) infection is characterized by a weak immune response to HBV. TLR 7 agonist has been reported to induce an innate cytokine response that suppresses HBV replication and to shape the adaptive immune response in chimpanzees. In the present study, we investigate the effect of SA-5 on immune activation against HBs antigen (Ag) using HBsAg transgenic mice lineage 107-5D.
Method
SA-5 was orally administered once a week for 4 weeks at 3 mg/kg. Serum sample was obtained twice a week. Liver tissue and splenocytes were obtained 7 days after the last SA-5 administration. Afterwards Immunohistochemistry and Enzyme-Linked ImmunoSpot (ELISPOT) assay followed.
Result
Serum level of alanine aminotransferase (ALT) increased in the following day of SA-5 administration but returned to the baseline 7days after. The positive cells of HBsAg immunohistochemistry significantly deceased in the SA-5 group compared with the control group. The SA5-treated mice mounted stronger cellular responses against HBsAg in ELISPOT assay and the spot number was negatively correlated with HBsAg immunohistochemistry positive cells.
Conclusion
SA5 may overcome immune tolerance in patients with chronic HBV infection.
- Index Term 1: HBV
- Index Term 2: HB vaccine