Strategies to Improve Efficacy of Therapeutic Vaccines for Chronic Hepatitis B Infection
Date Issued
2009
Date
2009
Author(s)
Tseng, Yo-Yu
Abstract
In chronic hepatitis B virus infection, patients usually cannot eliminate virus by immune response themselves. Therefore, developing the stratrgy to trigger the immune response of chronic hepatitis B patients against HBV infected liver cells is actively persuaded.herapeutic vaccine exhibits potent immune modulatory potentials and almost no side effects, but possesses little antiviral capacity and immune response in patients with chronic hepatitis B. However, reducing virus titer can enhance therapeutic vaccine efficacy, and acquire better immune response than in higher virus titer condition as well. Therefore, we tried to test whether performing the therapeutic vaccine after reducing virus titer in HBV transgenic mice can get more efficient response than those mice didn’t reduce virus titer.n our previously study published in 2007, using double-stranded adeno-associated virus 8-pseudotyped vector (dsAAV2/8) cantaining shRNA specific to HBV, especially HBV-S1 (dsAAV2/8/HBV-S1), can long-term inhibit the hepatitis B surface antigen (HBsAg) and HBV DNA in HBV transgenic mice. And the inhibition can be lasting for 120 days. Besides, dsAAV2/8/HBV-S1 almost clears the hepatitis B core Ag (HBcAg) of hepatocyte in transgenic mice.fter inhibiting virus titer in transgenic mice, we used DNA vaccine and adenovirus vaccine which encode HBcAg to immunize mice with DNA prime-adenovirus boost strategy. We found out this strategy can efficiently induce CD8+ T cell secreting IFN-γ. Meanwhile, we also choose several time points of immunization after HBV titer reduction. As vaccine administration was longer than 8 weeks after inhibiting virus titer, it showed no IFN-γ secreting response.espite of reducing HBV titer in transgenic mice in order to enhance vaccine efficacy, we also tried to improve vaccine ability by using adjuvants. Granulocyte/monocyte colony-stimulating factor (GM-CSF) is now considered as an important cytokine to make dendritic cell maturation. CD40 ligand (CD40L) is a costimulatory molecule major expressing on activated T cell. Therefore, we construted the expression vector that encodes CD40L/GM-CSF fusion protein as our vaccine adjuvant.e found that using plasmid encoding CD40L/GM-CSF fusion protein in cardiotoxin pretreated mice can efficiently enforce vaccine-induced antibody response. Additionly, it can improve T cell proliferation.n conclusion, reducing virus titer before vaccination will be a strategy worth studying. Meanwhile, combination of two adjuvants as a fusion protein might be an inspiring method to improve vaccine efficacy.
Subjects
Hepatitis B virus
therapeutic vaccine
adjuvant
granulocyte/monocyte colony-stimulating factor (GM-CSF)
CD40 ligand (CD40L)
fusion protein
SDGs
File(s)![Thumbnail Image]()
Loading...
Name
ntu-98-R96424012-1.pdf
Size
23.32 KB
Format
Adobe PDF
Checksum
(MD5):115a50c60f489b0e1812c5a948e68dee