Immunogenicity of an Intranasal Dual (Core and Surface)-Antigen Vaccine Against Hepatitis B Virus Enhanced by Carboxyl-Vinyl Polymer Excipients

Rashid, Md Haroon Or; Yasui, Fumihiko; Sanada, Takahiro; Kono, Risa; Honda, Tomoko; Kitab, Bouchra; Akter, Lipi; Utsunomiya, Masashi; Sato, Risa; Yoshida, Osamu; Hiasa, Yoichi; Oda, Yasunori; Goh, Yasumasa; Miyazaki, Takashi; Kohara, Michinori; Tsukiyama-Kohara, Kyoko

doi:10.3390/vaccines13050464

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Open AccessArticle

Immunogenicity of an Intranasal Dual (Core and Surface)-Antigen Vaccine Against Hepatitis B Virus Enhanced by Carboxyl-Vinyl Polymer Excipients

by

Md Haroon Or Rashid

¹,

Fumihiko Yasui

²,

Takahiro Sanada

²,

Risa Kono

²,

Tomoko Honda

²,

Bouchra Kitab

¹,

Lipi Akter

¹

,

Masashi Utsunomiya

¹,

Risa Sato

¹,

Osamu Yoshida

³,

Yoichi Hiasa

³

,

Yasunori Oda

⁴,

Yasumasa Goh

⁴,

Takashi Miyazaki

⁵,

Michinori Kohara

²

and

Kyoko Tsukiyama-Kohara

^1,*

¹

Joint Faculty of Veterinary Medicine, Kagoshima University, Kagoshima 890-0065, Japan

²

Department of Microbiology and Cell Biology, Tokyo Metropolitan Institute of Medical Science, Tokyo 156-8506, Japan

³

Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Toon 791-0295, Japan

⁴

Beacle Co., Ltd.; Kyoto 606-8305, Japan

⁵

Toko Yakuhin Kogyo Co, Ltd.; Toyama 930-0211, Japan

^*

Author to whom correspondence should be addressed.

Vaccines 2025, 13(5), 464; https://doi.org/10.3390/vaccines13050464

Submission received: 4 March 2025 / Revised: 18 April 2025 / Accepted: 24 April 2025 / Published: 25 April 2025

(This article belongs to the Section Hepatitis Virus Vaccines)

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Abstract

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 µg of hy-LHBs and 2.5 or 10 µg 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-γ 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 µg/antigen, but only a non-significant elevation was noted with the vaccine containing 2.5 µg HBc. The BioPlex assay showed a significant increase in IL-2 (#00-07, 0B), IL-12(p40)(#00), eotaxin (#00), MIP1α (#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.

Keywords: HBV; CVP; hy-LHBs; HBc

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MDPI and ACS Style

Rashid, M.H.O.; Yasui, F.; Sanada, T.; Kono, R.; Honda, T.; Kitab, B.; Akter, L.; Utsunomiya, M.; Sato, R.; Yoshida, O.; et al. Immunogenicity of an Intranasal Dual (Core and Surface)-Antigen Vaccine Against Hepatitis B Virus Enhanced by Carboxyl-Vinyl Polymer Excipients. Vaccines 2025, 13, 464. https://doi.org/10.3390/vaccines13050464

AMA Style

Rashid MHO, Yasui F, Sanada T, Kono R, Honda T, Kitab B, Akter L, Utsunomiya M, Sato R, Yoshida O, et al. Immunogenicity of an Intranasal Dual (Core and Surface)-Antigen Vaccine Against Hepatitis B Virus Enhanced by Carboxyl-Vinyl Polymer Excipients. Vaccines. 2025; 13(5):464. https://doi.org/10.3390/vaccines13050464

Chicago/Turabian Style

Rashid, Md Haroon Or, Fumihiko Yasui, Takahiro Sanada, Risa Kono, Tomoko Honda, Bouchra Kitab, Lipi Akter, Masashi Utsunomiya, Risa Sato, Osamu Yoshida, and et al. 2025. "Immunogenicity of an Intranasal Dual (Core and Surface)-Antigen Vaccine Against Hepatitis B Virus Enhanced by Carboxyl-Vinyl Polymer Excipients" Vaccines 13, no. 5: 464. https://doi.org/10.3390/vaccines13050464

APA Style

Rashid, M. H. O., Yasui, F., Sanada, T., Kono, R., Honda, T., Kitab, B., Akter, L., Utsunomiya, M., Sato, R., Yoshida, O., Hiasa, Y., Oda, Y., Goh, Y., Miyazaki, T., Kohara, M., & Tsukiyama-Kohara, K. (2025). Immunogenicity of an Intranasal Dual (Core and Surface)-Antigen Vaccine Against Hepatitis B Virus Enhanced by Carboxyl-Vinyl Polymer Excipients. Vaccines, 13(5), 464. https://doi.org/10.3390/vaccines13050464

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Immunogenicity of an Intranasal Dual (Core and Surface)-Antigen Vaccine Against Hepatitis B Virus Enhanced by Carboxyl-Vinyl Polymer Excipients

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