{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:37:21Z","timestamp":1760060241208,"version":"build-2065373602"},"reference-count":29,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2025,8,12]],"date-time":"2025-08-12T00:00:00Z","timestamp":1754956800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Viravaxx AG","award":["FA648A0312"],"award-info":[{"award-number":["FA648A0312"]}]},{"name":"Danube Allergy Research Cluster of the country of Lower Austria","award":["FA648A0312"],"award-info":[{"award-number":["FA648A0312"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>Background: Chronic hepatitis B (CHB) remains being a major public health threat, and currently existing CHB therapies have limited efficacy and side effects. We have recently developed a vaccine termed VVX001 based on a recombinant fusion protein consisting of the preS domain of the large surface protein of hepatitis B virus (HBV) fused to grass pollen allergen peptides. VVX001 has been shown to induce preS-specific antibodies in grass pollen allergic patients, and sera of immunized subjects inhibited HBV infection in vitro. Methods: In this study we investigated if immunization with VVX001 can induce preS-specific antibodies in CHB using the adeno-associated virus (AAV)-HBV murine model of CHB. Six groups of C57BL\/6 female mice (n = 6) were transduced with AAV-HBV or AAV-Empty, and after six weeks, they were immunized five times with 20 \u00b5g of aluminum hydroxide-adsorbed VVX001 or preS or vehicle (Alum alone). Serum samples were taken continuously. Two weeks after the last immunization, spleen and liver mononuclear cells were collected. Serum reactivity to preS and preS-derived peptides was assessed by ELISA. B-cell responses were measured by ELISPOT assay, and intrahepatic lymphocyte (ILH) counts were determined by FACS. HBV DNA, HBsAg, HBeAg, ALT, and AST were assessed using commercial kits. Results: Our results show that VVX001 induces preS-specific IgG antibodies that cross-react with different HBV genotypes A-H and are directed against the sodium taurocholate co-transporting polypeptide (NTCP) receptor binding site of preS both in mice with and without HBV. Actively immunized AAV-HBV-treated mice had a higher number of intrahepatic lymphocytes than vehicle-vaccinated and mock-transduced animals. Conclusions: These findings encourage performing further trials to study the potential of VVX001 for therapeutic vaccination against CHB.<\/jats:p>","DOI":"10.3390\/vaccines13080854","type":"journal-article","created":{"date-parts":[[2025,8,13]],"date-time":"2025-08-13T07:45:31Z","timestamp":1755071131000},"page":"854","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["VVX001 Induces preS-Specific Antibodies Reacting to Common HBV Genotypes in Hepatitis B Virus (HBV) Carrier Mice"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5825-2687","authenticated-orcid":false,"given":"Inna","family":"Tulaeva","sequence":"first","affiliation":[{"name":"Institute of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, 1090 Vienna, Austria"},{"name":"Laboratory of Immunopathology, Department of Clinical Immunology and Allergology, I. M. Sechenov First Moscow State Medical University, 119991 Moscow, Russia"},{"name":"Life Improvement by Future Technologies (LIFT) Center, 115478 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8850-8073","authenticated-orcid":false,"given":"Maryline","family":"Bourgine","sequence":"additional","affiliation":[{"name":"Virology Department, Institut Pasteur, Universit\u00e9 Paris Cit\u00e9, 75015 Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carolin","family":"Cornelius-Nikl","sequence":"additional","affiliation":[{"name":"Institute of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexander","family":"Karaulov","sequence":"additional","affiliation":[{"name":"Laboratory of Immunopathology, Department of Clinical Immunology and Allergology, I. M. Sechenov First Moscow State Medical University, 119991 Moscow, Russia"},{"name":"Life Improvement by Future Technologies (LIFT) Center, 115478 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rainer","family":"Henning","sequence":"additional","affiliation":[{"name":"Viravaxx AG, 1190 Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1231-845X","authenticated-orcid":false,"given":"Marie-Louise","family":"Michel","sequence":"additional","affiliation":[{"name":"Virology Department, Institut Pasteur, Universit\u00e9 Paris Cit\u00e9, 75015 Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rudolf","family":"Valenta","sequence":"additional","affiliation":[{"name":"Institute of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, 1090 Vienna, Austria"},{"name":"Laboratory of Immunopathology, Department of Clinical Immunology and Allergology, I. M. Sechenov First Moscow State Medical University, 119991 Moscow, Russia"},{"name":"Life Improvement by Future Technologies (LIFT) Center, 115478 Moscow, Russia"},{"name":"Center for Molecular Allergology, Karl Landsteiner University of Health Sciences, 3500 Krems, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1743-422X-10-239","article-title":"Medical Virology of Hepatitis B: How It Began and Where We Are Now","volume":"10","author":"Gerlich","year":"2013","journal-title":"Virol. J."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1016\/S2468-1253(19)30119-0","article-title":"A Global Scientific Strategy to Cure Hepatitis B","volume":"4","author":"Revill","year":"2019","journal-title":"Lancet Gastroenterol. Hepatol."},{"key":"ref_3","unstructured":"World Health Organization (2024). 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