Intranasal HBsAg/HBcAg-Containing Vaccine Induces Neutralizing Anti-HBs Production in Hepatitis B Vaccine Non-Responders
Hepatitis B vaccine induces the production of antibodies against hepatitis B surface antigen (anti-HBs) and prevents hepatitis B virus (HBV) infection. However, 5–10% of individuals cannot develop anti-HBs even after multiple vaccinations (HB vaccine non-responders). We developed an intranasal vacci...
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MDPI AG
2023-09-01
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author | Kana Shiraishi Osamu Yoshida Yusuke Imai Sheikh Mohammad Fazle Akbar Takahiro Sanada Michinori Kohara Takashi Miyazaki Taizou Kamishita Teruki Miyake Masashi Hirooka Yoshio Tokumoto Masanori Abe Julio Cesar Aguilar Rubido Gerardo Guillen Nieto Yoichi Hiasa |
author_facet | Kana Shiraishi Osamu Yoshida Yusuke Imai Sheikh Mohammad Fazle Akbar Takahiro Sanada Michinori Kohara Takashi Miyazaki Taizou Kamishita Teruki Miyake Masashi Hirooka Yoshio Tokumoto Masanori Abe Julio Cesar Aguilar Rubido Gerardo Guillen Nieto Yoichi Hiasa |
author_sort | Kana Shiraishi |
collection | DOAJ |
description | Hepatitis B vaccine induces the production of antibodies against hepatitis B surface antigen (anti-HBs) and prevents hepatitis B virus (HBV) infection. However, 5–10% of individuals cannot develop anti-HBs even after multiple vaccinations (HB vaccine non-responders). We developed an intranasal vaccine containing both HBs antigen (HBsAg) and HB core antigen (HBcAg) and mixed it with a viscosity enhancer, carboxyl vinyl polymer (CVP-NASVAC). Here, we investigated the prophylactic capacity of CVP-NASVAC in HB vaccine non-responders. Thirty-four HB vaccine non-responders were administered three doses of intranasal CVP-NASVAC. The prophylactic capacity of CVP-NASVAC was assessed by evaluating the induction of anti-HBs and anti-HBc (IgA and IgG) production, HBV-neutralization activity of sera, and induction of HBs- and HBc-specific cytotoxic T lymphocytes (CTLs). After CVP-NASVAC administration, anti-HBs and anti-HBc production were induced in 31/34 and 27/34 patients, respectively. IgA anti-HBs and anti-HBc titers significantly increased after CVP-NASVAC vaccination. HBV-neutralizing activity in vitro was confirmed in the sera of 26/29 CVP-NASVAC-administered participants. HBs- and HBc-specific CTL counts substantially increased after the CVP-NASVAC administration. Mild adverse events were observed in 9/34 participants; no serious adverse events were reported. Thus, CVP-NASVAC could be a beneficial vaccine for HB vaccine non-responders. |
first_indexed | 2024-03-10T21:52:12Z |
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issn | 2076-393X |
language | English |
last_indexed | 2024-03-10T21:52:12Z |
publishDate | 2023-09-01 |
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spelling | doaj.art-198fc98d553b4e0e9cc98cbf8ac411b92023-11-19T13:19:32ZengMDPI AGVaccines2076-393X2023-09-01119147910.3390/vaccines11091479Intranasal HBsAg/HBcAg-Containing Vaccine Induces Neutralizing Anti-HBs Production in Hepatitis B Vaccine Non-RespondersKana Shiraishi0Osamu Yoshida1Yusuke Imai2Sheikh Mohammad Fazle Akbar3Takahiro Sanada4Michinori Kohara5Takashi Miyazaki6Taizou Kamishita7Teruki Miyake8Masashi Hirooka9Yoshio Tokumoto10Masanori Abe11Julio Cesar Aguilar Rubido12Gerardo Guillen Nieto13Yoichi Hiasa14Department of Gastroenterology and Metabology, Graduate School of Medicine, Ehime University, Toon 791-0295, JapanDepartment of Gastroenterology and Metabology, Graduate School of Medicine, Ehime University, Toon 791-0295, JapanDepartment of Gastroenterology and Metabology, Graduate School of Medicine, Ehime University, Toon 791-0295, JapanDepartment of Gastroenterology and Metabology, Graduate School of Medicine, Ehime University, Toon 791-0295, JapanDepartment of Microbiology and Cell Biology, Tokyo Metropolitan Institute of Medical Science, Tokyo 156-8506, JapanDepartment of Microbiology and Cell Biology, Tokyo Metropolitan Institute of Medical Science, Tokyo 156-8506, JapanToko Yakuhin Kogyo Co., Ltd., Osaka 530-0022, JapanToko Yakuhin Kogyo Co., Ltd., Osaka 530-0022, JapanDepartment of Gastroenterology and Metabology, Graduate School of Medicine, Ehime University, Toon 791-0295, JapanDepartment of Gastroenterology and Metabology, Graduate School of Medicine, Ehime University, Toon 791-0295, JapanDepartment of Gastroenterology and Metabology, Graduate School of Medicine, Ehime University, Toon 791-0295, JapanDepartment of Gastroenterology and Metabology, Graduate School of Medicine, Ehime University, Toon 791-0295, JapanVaccine Division, Biomedical Research Department, Center for Genetic Engineering and Biotechnology, Havana 10600, CubaVaccine Division, Biomedical Research Department, Center for Genetic Engineering and Biotechnology, Havana 10600, CubaDepartment of Gastroenterology and Metabology, Graduate School of Medicine, Ehime University, Toon 791-0295, JapanHepatitis B vaccine induces the production of antibodies against hepatitis B surface antigen (anti-HBs) and prevents hepatitis B virus (HBV) infection. However, 5–10% of individuals cannot develop anti-HBs even after multiple vaccinations (HB vaccine non-responders). We developed an intranasal vaccine containing both HBs antigen (HBsAg) and HB core antigen (HBcAg) and mixed it with a viscosity enhancer, carboxyl vinyl polymer (CVP-NASVAC). Here, we investigated the prophylactic capacity of CVP-NASVAC in HB vaccine non-responders. Thirty-four HB vaccine non-responders were administered three doses of intranasal CVP-NASVAC. The prophylactic capacity of CVP-NASVAC was assessed by evaluating the induction of anti-HBs and anti-HBc (IgA and IgG) production, HBV-neutralization activity of sera, and induction of HBs- and HBc-specific cytotoxic T lymphocytes (CTLs). After CVP-NASVAC administration, anti-HBs and anti-HBc production were induced in 31/34 and 27/34 patients, respectively. IgA anti-HBs and anti-HBc titers significantly increased after CVP-NASVAC vaccination. HBV-neutralizing activity in vitro was confirmed in the sera of 26/29 CVP-NASVAC-administered participants. HBs- and HBc-specific CTL counts substantially increased after the CVP-NASVAC administration. Mild adverse events were observed in 9/34 participants; no serious adverse events were reported. Thus, CVP-NASVAC could be a beneficial vaccine for HB vaccine non-responders.https://www.mdpi.com/2076-393X/11/9/1479hepatitis B viruscellular immunityimmunoglobulin Ainfectious diseasecarboxyl vinyl polymer |
spellingShingle | Kana Shiraishi Osamu Yoshida Yusuke Imai Sheikh Mohammad Fazle Akbar Takahiro Sanada Michinori Kohara Takashi Miyazaki Taizou Kamishita Teruki Miyake Masashi Hirooka Yoshio Tokumoto Masanori Abe Julio Cesar Aguilar Rubido Gerardo Guillen Nieto Yoichi Hiasa Intranasal HBsAg/HBcAg-Containing Vaccine Induces Neutralizing Anti-HBs Production in Hepatitis B Vaccine Non-Responders Vaccines hepatitis B virus cellular immunity immunoglobulin A infectious disease carboxyl vinyl polymer |
title | Intranasal HBsAg/HBcAg-Containing Vaccine Induces Neutralizing Anti-HBs Production in Hepatitis B Vaccine Non-Responders |
title_full | Intranasal HBsAg/HBcAg-Containing Vaccine Induces Neutralizing Anti-HBs Production in Hepatitis B Vaccine Non-Responders |
title_fullStr | Intranasal HBsAg/HBcAg-Containing Vaccine Induces Neutralizing Anti-HBs Production in Hepatitis B Vaccine Non-Responders |
title_full_unstemmed | Intranasal HBsAg/HBcAg-Containing Vaccine Induces Neutralizing Anti-HBs Production in Hepatitis B Vaccine Non-Responders |
title_short | Intranasal HBsAg/HBcAg-Containing Vaccine Induces Neutralizing Anti-HBs Production in Hepatitis B Vaccine Non-Responders |
title_sort | intranasal hbsag hbcag containing vaccine induces neutralizing anti hbs production in hepatitis b vaccine non responders |
topic | hepatitis B virus cellular immunity immunoglobulin A infectious disease carboxyl vinyl polymer |
url | https://www.mdpi.com/2076-393X/11/9/1479 |
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