{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T21:30:04Z","timestamp":1790371804106,"version":"4.1.0"},"reference-count":46,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2023,5,25]],"date-time":"2023-05-25T00:00:00Z","timestamp":1684972800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Chinese National Natural Science Foundation","award":["81991492"],"award-info":[{"award-number":["81991492"]}]},{"name":"Chinese National Natural Science Foundation","award":["82041039"],"award-info":[{"award-number":["82041039"]}]},{"name":"Chinese National Natural Science Foundation","award":["2021YFC2302500"],"award-info":[{"award-number":["2021YFC2302500"]}]},{"name":"Chinese National Natural Science Foundation","award":["ZD2021CY001"],"award-info":[{"award-number":["ZD2021CY001"]}]},{"name":"Ministry of Science and Technology of China","award":["81991492"],"award-info":[{"award-number":["81991492"]}]},{"name":"Ministry of Science and Technology of China","award":["82041039"],"award-info":[{"award-number":["82041039"]}]},{"name":"Ministry of Science and Technology of China","award":["2021YFC2302500"],"award-info":[{"award-number":["2021YFC2302500"]}]},{"name":"Ministry of Science and Technology of China","award":["ZD2021CY001"],"award-info":[{"award-number":["ZD2021CY001"]}]},{"name":"Shanghai Municipal Science and Technology Major Project","award":["81991492"],"award-info":[{"award-number":["81991492"]}]},{"name":"Shanghai Municipal Science and Technology Major Project","award":["82041039"],"award-info":[{"award-number":["82041039"]}]},{"name":"Shanghai Municipal Science and Technology Major Project","award":["2021YFC2302500"],"award-info":[{"award-number":["2021YFC2302500"]}]},{"name":"Shanghai Municipal Science and Technology Major Project","award":["ZD2021CY001"],"award-info":[{"award-number":["ZD2021CY001"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>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-\u03b1+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 \u03bcg\/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+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+ 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.<\/jats:p>","DOI":"10.3390\/vaccines11061026","type":"journal-article","created":{"date-parts":[[2023,5,26]],"date-time":"2023-05-26T01:52:43Z","timestamp":1685065963000},"page":"1026","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Mafosfamide Boosts GMI-HBVac against HBV via Treg Depletion in HBV-Infected Mice"],"prefix":"10.3390","volume":"11","author":[{"given":"Qin","family":"Lin","sequence":"first","affiliation":[{"name":"Key Laboratory of Medical Molecular Virology (MOE\/NHC\/CAMS), Shanghai Frontiers Science Center of Pathogenic Microorganisms and Infection, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiwei","family":"Zhong","sequence":"additional","affiliation":[{"name":"Key Laboratory of Medical Molecular Virology (MOE\/NHC\/CAMS), Shanghai Frontiers Science Center of Pathogenic Microorganisms and Infection, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China"},{"name":"Shanghai Institute of Infectious Disease and Biosecurity, Fudan University, Shanghai 200032, China"},{"name":"National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai 200040, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9945-1818","authenticated-orcid":false,"given":"Bin","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Medical Molecular Virology (MOE\/NHC\/CAMS), Shanghai Frontiers Science Center of Pathogenic Microorganisms and Infection, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China"},{"name":"Shanghai Institute of Infectious Disease and Biosecurity, Fudan University, Shanghai 200032, China"},{"name":"National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai 200040, China"},{"name":"Children\u2019s Hospital of Fudan University, Shanghai 201102, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,5,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1225","DOI":"10.1053\/jhep.2001.29401","article-title":"Chronic hepatitis B","volume":"34","author":"Lok","year":"2001","journal-title":"Hepatology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"796","DOI":"10.1016\/S2468-1253(22)00124-8","article-title":"(GBD 2019 Hepatitis B Collaborators) Global, regional, and national burden of hepatitis B, 1990\u20132019: A systematic analysis for the Global Burden of Disease Study 2019","volume":"7","author":"Sheena","year":"2022","journal-title":"Lancet Gastroenterol. 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