Article
Version 1
Preserved in Portico This version is not peer-reviewed
Mafosfamide combine with GMI-HBVac against HBV via Treg depletion in HBV-infected mice
Version 1
: Received: 5 March 2023 / Approved: 6 March 2023 / Online: 6 March 2023 (03:37:38 CET)
A peer-reviewed article of this Preprint also exists.
Lin, Q.; Zhong, Y.; Wang, B. Mafosfamide Boosts GMI-HBVac against HBV via Treg Depletion in HBV-Infected Mice. Vaccines 2023, 11, 1026. Lin, Q.; Zhong, Y.; Wang, B. Mafosfamide Boosts GMI-HBVac against HBV via Treg Depletion in HBV-Infected Mice. Vaccines 2023, 11, 1026.
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 in the host. Theoretically, suppression of Treg 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 determine the efficacy of anti-CHB, 2ug/ml MAF was combined with the GMI-HBVac in an HBV-infected animal model as an anti-Treg treatment. 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 upregulation of IFN-gamma producing CD8+T cells. In addition, MAF+GMI-HBVac vaccination stimulates T cell infiltration in HBV-infected liver. These conditions may contribute to an enhanced immune response and the clearance of HBV-associated antigens, including serum HBsAg, serum HBcAg, and HBcAg+ hepatocytes. Overall, this is the first indication that MAF was utilized as an adjuvant to deplete Tregs and paired with GMI-HBVac as a unique therapeutic vaccine regimen against established CHB mice to produce a functional cure, as seen by the remarkable clearance of HBsAg.
Keywords
Chronic hepatitis B infection; Therapeutic vaccines; Regulatory T cells; Functional cure; GMI-HBVac; Mafosfamide
Subject
Biology and Life Sciences, Immunology and Microbiology
Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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