{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:12:25Z","timestamp":1760058745332,"version":"build-2065373602"},"reference-count":34,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2025,4,25]],"date-time":"2025-04-25T00:00:00Z","timestamp":1745539200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Japan Agency for Medical Research and Development","award":["20fk0210033h0003","23fk0210083h0003","24fk0210143s0201"],"award-info":[{"award-number":["20fk0210033h0003","23fk0210083h0003","24fk0210143s0201"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>Background: Hepatitis B virus (HBV) is a major cause of morbidity and mortality globally, and chronic infections are associated with cirrhosis and hepatocellular carcinoma. Issues with conventional treatments and vaccines mean there is a need for new therapeutic vaccines, which must elicit a strong and sustainable immune response. Here, we evaluated the immunogenicity of dual-antigen vaccines containing hybrid surface (hy-LHBs) and core (HBc) antigens, combined with a carboxyl-vinyl polymer (CVP) as a mucoadhesive excipient, following intranasal administration in mice. Methods: Mice were intranasally administered a mixed vaccine (10 \u00b5g of hy-LHBs and 2.5 or 10 \u00b5g of HBc) with or without a CVP excipient, and they were assessed for their immune response (levels of IgGs or IgA antibodies in an ELISA, IFN-\u03b3 level in splenocytes in an ELISpot assay, and cytokine\/chemokine levels in a BioPlex assay). A protein stability assay was also conducted for vaccine formulations with and without excipients. Results: Significantly enhanced IgG production was noted targeting hy-LHBs and (less markedly) HBc at 10 \u00b5g\/antigen, but only a non-significant elevation was noted with the vaccine containing 2.5 \u00b5g HBc. The BioPlex assay showed a significant increase in IL-2 (#00-07, 0B), IL-12(p40)(#00), eotaxin (#00), MIP1\u03b1 (#00, #00-07, 0B), and MCP-1 (#00-07, 0B) in mice that received treatment compared to those of untreated mice. The endpoint titers of IgG1 and IgG2a were measured, which were higher with CVP excipients than without. From the IgG2a\/IgG1 ratio, a higher IgG1 response was induced by CVPs to hy-LHBs and a higher IgG2a response was induced to HBc. Th2-dominant phenotype to hy-LHBs was induced with CVP#00 in an ELISpot assay. The highest anti-hy-LHBs antibody titer was noted with the conventional CVP#00 excipient. Consistent with these results, a higher amount of neutralizing antibodies of HBV was induced with CVP#00 treatment and followed by #00-03 and #14-00. Conclusions: We consider that the addition of CVP excipients to vaccine formulation enhances immunogenicity and HBV antigen stability for intranasal vaccines. This effect was seen for both humoral and cell-mediated immune responses, indicating the potential of CVPs as excipients in intranasal HBV vaccines.<\/jats:p>","DOI":"10.3390\/vaccines13050464","type":"journal-article","created":{"date-parts":[[2025,4,25]],"date-time":"2025-04-25T10:42:09Z","timestamp":1745577729000},"page":"464","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Immunogenicity of an Intranasal Dual (Core and Surface)-Antigen Vaccine Against Hepatitis B Virus Enhanced by Carboxyl-Vinyl Polymer Excipients"],"prefix":"10.3390","volume":"13","author":[{"given":"Md Haroon Or","family":"Rashid","sequence":"first","affiliation":[{"name":"Joint Faculty of Veterinary Medicine, Kagoshima University, Kagoshima 890-0065, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fumihiko","family":"Yasui","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Cell Biology, Tokyo Metropolitan Institute of Medical Science, Tokyo 156-8506, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takahiro","family":"Sanada","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Cell Biology, Tokyo Metropolitan Institute of Medical Science, Tokyo 156-8506, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Risa","family":"Kono","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Cell Biology, Tokyo Metropolitan Institute of Medical Science, Tokyo 156-8506, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomoko","family":"Honda","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Cell Biology, Tokyo Metropolitan Institute of Medical Science, Tokyo 156-8506, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bouchra","family":"Kitab","sequence":"additional","affiliation":[{"name":"Joint Faculty of Veterinary Medicine, Kagoshima University, Kagoshima 890-0065, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6317-9410","authenticated-orcid":false,"given":"Lipi","family":"Akter","sequence":"additional","affiliation":[{"name":"Joint Faculty of Veterinary Medicine, Kagoshima University, Kagoshima 890-0065, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masashi","family":"Utsunomiya","sequence":"additional","affiliation":[{"name":"Joint Faculty of Veterinary Medicine, Kagoshima University, Kagoshima 890-0065, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Risa","family":"Sato","sequence":"additional","affiliation":[{"name":"Joint Faculty of Veterinary Medicine, Kagoshima University, Kagoshima 890-0065, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Osamu","family":"Yoshida","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Toon 791-0295, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4117-339X","authenticated-orcid":false,"given":"Yoichi","family":"Hiasa","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Toon 791-0295, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasunori","family":"Oda","sequence":"additional","affiliation":[{"name":"Beacle Co., Ltd., Kyoto 606-8305, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasumasa","family":"Goh","sequence":"additional","affiliation":[{"name":"Beacle Co., Ltd., Kyoto 606-8305, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takashi","family":"Miyazaki","sequence":"additional","affiliation":[{"name":"Toko Yakuhin Kogyo Co., Ltd., Toyama 930-0211, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2130-5837","authenticated-orcid":false,"given":"Michinori","family":"Kohara","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Cell Biology, Tokyo Metropolitan Institute of Medical Science, Tokyo 156-8506, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4403-2018","authenticated-orcid":false,"given":"Kyoko","family":"Tsukiyama-Kohara","sequence":"additional","affiliation":[{"name":"Joint Faculty of Veterinary Medicine, Kagoshima University, Kagoshima 890-0065, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"101938","DOI":"10.1016\/j.eclinm.2023.101938","article-title":"Global prevalence of hepatitis B or hepatitis C infection among patients with tuberculosis 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