A hepatitis B virus-derived peptide combined with HBsAg exerts an anti-HBV effect in an HBV transgenic mouse model as a therapeutic vaccine

Yu-Min Choi; Dong Hyun Kim; Junghwa Jang; Bum-Joon Kim

doi:10.3389/fimmu.2023.1155637

A hepatitis B virus-derived peptide combined with HBsAg exerts an anti-HBV effect in an HBV transgenic mouse model as a therapeutic vaccine

Front Immunol. 2023 Jun 2:14:1155637. doi: 10.3389/fimmu.2023.1155637. eCollection 2023.

Authors

Yu-Min Choi¹, Dong Hyun Kim¹, Junghwa Jang¹, Bum-Joon Kim^{1

2

3

4

5}

Affiliations

¹ Department of Microbiology and Immunology, College of Medicine, Seoul National University, Seoul, Republic of Korea.
² Department of Biomedical Sciences, College of Medicine, Seoul National University, Seoul, Republic of Korea.
³ Liver Research Institute, College of Medicine, Seoul National University, Seoul, Republic of Korea.
⁴ Cancer Research Institute, College of Medicine, Seoul National University, Seoul, Republic of Korea.
⁵ Department of Microbiology and Immunology, Seoul National University Medical Research Center (SNUMRC), Seoul, Republic of Korea.

Abstract

Introduction: For complete or functional cure of hepatitis B virus (HBV) infection, application of immunotherapy is now being attempted. Recently, we reported that a 6-mer hepatitis B virus (HBV)-derived peptide, Poly6, exerts a strong anticancer effect in tumor-implanted mice through inducible nitric oxide synthase (iNOS)-producing DCs (Tip-DCs) in a type 1 interferon (IFN-I)-dependent manner, suggesting its potential as a vaccine adjuvant.

Methods: In this study, we explored the potential of Poly6 in combination with HBsAg as a therapeutic vaccine against hepatitis B virus infection. We investigated the immunotherapeutic potential of Poly6 combined with HBsAg vaccination against hepatitis B virus infection in C57BL/6 mice or an HBV transgenic mouse model.

Results: In C57BL/6 mice, Poly6 enhanced DC maturation and DC migration capacity in an IFN-I-dependent manner. Moreover, the addition of Poly6 to alum in combination with HBsAg also led to enhanced HBsAg-specific cell-mediated immune (CMI) responses, suggesting its potential as an adjuvant of HBsAg-based vaccines. In HBV transgenic mice, vaccination with Poly6 combined with HBsAg exerted a strong anti-HBV effect via induction of HBV-specific humoral and cell-mediated immune responses. In addition, it also induced HBV-specific effector memory T cells (T_EM).

Discussion: Our data indicated that vaccination with Poly6 in combination with HBsAg exerts an anti-HBV effect in HBV transgenic mice, which is mainly mediated by HBV-specific CMI and humoral immune responses via IFN-I-dependent DC activation, suggesting the feasibility of Poly6 as an adjuvant for an HBV therapeutic vaccine.

Keywords: (HBV)-derived peptide; DC maturation; Poly6; adjuvant; cell mediated immune (CMI) response; hepatitis B virus (HBV); therapeutic vaccination; type 1 interferon (IFN-I).

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adjuvants, Immunologic / pharmacology
Animals
Hepatitis B Surface Antigens
Hepatitis B Vaccines
Hepatitis B virus*
Hepatitis B*
Mice
Mice, Inbred C57BL
Mice, Transgenic

Substances

Hepatitis B Surface Antigens
Hepatitis B Vaccines
Adjuvants, Immunologic

Grants and funding

This research was supported by a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant no. HI22C0476). JJ received a scholarship from the BK21-plus education program provided by the National Research Foundation of Korea.