{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T12:57:32Z","timestamp":1789131452207,"version":"build-2803163510"},"reference-count":54,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T00:00:00Z","timestamp":1773273600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>\n                    Therapeutic vaccines offer hope for a curative treatment of chronic hepatitis B virus (HBV) infection. We developed a therapeutic hepatitis B vaccine,\n                    <jats:italic>TherVacB<\/jats:italic>\n                    , which employs priming with adjuvanted HBV S (HBsAg) and Core antigens of a single genotype, and a boost with a pan-genotypic Modified Vaccinia Ankara vector (MVA-HBVac) expressing several viral proteins that cover more than 95% of HBV circulating strains. Priming immunization with antigens exactly matching those expressed by the MVA may improve the efficacy of\n                    <jats:italic>TherVacB<\/jats:italic>\n                    . However, recombinant protein antigens need to be produced separately and require complex and costly purification, as well as a Th1-inducing adjuvant, to elicit CD8\n                    <jats:sup>+<\/jats:sup>\n                    T-cell responses. These limitations may be overcome by DNA vaccines, which enable the direct expression of several antigens\n                    <jats:italic>in vivo<\/jats:italic>\n                    . Here, we investigated the potential of DNA vaccination as an alternative to protein priming to broaden and enhance HBV-specific immunity. Immunization of HBV-carrier mice with a DNA prime-MVA boost regimen elicited robust HBV-specific CD8\n                    <jats:sup>+<\/jats:sup>\n                    T-cell responses, capable of reducing serum HBeAg levels and eliminating HBV-infected hepatocytes. However, it yielded poor neutralizing anti-HBs titers, resulting in an inefficient reduction of circulating HBsAg. Including adjuvanted HBsAg into DNA priming, either simultaneously or sequentially, significantly enhanced HBsAg-to-anti-HBs seroconversion rates. Still, only the sequential application supported vigorous plasmid-mediated CD8\n                    <jats:sup>+<\/jats:sup>\n                    T-cell immunity. Interestingly, sequential immunization with DNA, followed by HBsAg and MVA, elicited neutralizing anti-HBs antibodies and enhanced HBV-specific CD8\n                    <jats:sup>+<\/jats:sup>\n                    T-cell responses, resulting in a more potent antiviral effect compared to the reverse priming regimen. Our study demonstrates that although DNA can successfully prime an effective antiviral CD8\n                    <jats:sup>+<\/jats:sup>\n                    T-cell response, it requires additional immunization with adjuvanted HBsAg to elicit satisfactory neutralizing antibody titers. In addition, it demonstrates that the sequence of immunizations in multicomponent heterologous-prime boost regimens is crucial and can significantly affect the quantity and quality of induced immune responses.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2026.1771887","type":"journal-article","created":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T06:46:47Z","timestamp":1773298007000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Therapeutic hepatitis B vaccine employing DNA prime \u2013 MVA boost scheme requires additional priming with recombinant HBsAg to elicit an adequate antibody response"],"prefix":"10.3389","volume":"17","author":[{"given":"H\u00e9l\u00e8ne A.","family":"Kerth","sequence":"first","affiliation":[{"name":"Institute of Virology, School of Medicine and Health, Technical University of Munich\/Helmholtz Munich","place":["Munich, Germany"]},{"name":"German Center for Infection 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