Back to Search
Start Over
Mafosfamide Boosts GMI-HBVac against HBV via Treg Depletion in HBV-Infected Mice.
- Source :
- Vaccines; Jun2023, Vol. 11 Issue 6, p1026, 22p
- Publication Year :
- 2023
-
Abstract
- Chronic hepatitis B infection remains a significant worldwide health burden, placing persons at risk for hepatocellular cancer and hepatic fibrosis. Chronic hepatitis B virus (CHB) infection is characterized by elevated levels of immunosuppressive regulatory T cells (Tregs), which can inhibit the function of effector T cells and lead to an insufficient immune clearance response against HBV. Theoretically, suppression of Treg cell functionality and percentage could increase anti-HBV reactivity in CHB-infected patients, although this has not yet been explored. We attempted to enhance our previously established anti-CHB protocol utilizing the GM-CSF+IFN-α+rHBVvac regimen (GMI-HBVac) by incorporating mafosfamide (MAF), which has been utilized in anticancer therapy in the past. Intravenous administration of MAF to rAAV8-1.3HBV-infected mice resulted in a dose-dependent reduction of Tregs in the blood, rebounding to pretreatment levels 10 days later. To assess the potential benefit of adding MAF to the anti-CHB protocol, 2 μg/mL MAF was combined with the GMI-HBVac as an anti-Treg treatment in an HBV-infected animal model. When rAAV8-1.3HBV-infected mice were immunized with MAF+GMI-HBVac, peripheral blood Tregs decreased significantly, leading to dendritic cell activation, HBV-specific T cell proliferation, and the upregulation of IFN-gamma-producing CD8<superscript>+</superscript>T cells. In addition, MAF+GMI-HBVac vaccination stimulated T cell infiltration in HBV-infected livers. These effects may contribute to an enhanced immune response and the clearance of HBV-associated antigens, including serum HBsAg, serum HBcAg, and HBcAg<superscript>+</superscript> hepatocytes. Overall, this is the first indication that MAF can act as an adjuvant with GMI-HBVac to deplete Tregs in mice with an established CHB infection. This unique therapeutic vaccine regimen produced a functional cure, as revealed by the remarkable clearance of HBsAg. [ABSTRACT FROM AUTHOR]
- Subjects :
- REGULATORY T cells
CHRONIC hepatitis B
T cells
HEPATITIS B virus
HEPATIC fibrosis
Subjects
Details
- Language :
- English
- ISSN :
- 2076393X
- Volume :
- 11
- Issue :
- 6
- Database :
- Complementary Index
- Journal :
- Vaccines
- Publication Type :
- Academic Journal
- Accession number :
- 164688185
- Full Text :
- https://doi.org/10.3390/vaccines11061026