Immune Profiles Elicited by Different HBV Vaccine Modalities and Their Associations with Serological and Intrahepatic Viral Outcomes.
6 affiliations
- 1Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China.
- 2Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Shanghai Medical College, Fudan University, Shanghai 200032, China.
- 3Shanghai Institute of Infectious Disease and Biosecurity, Fudan University, Shanghai 200032, China.
- 4Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai 200040, China.
- 5Laboratory of Medical Molecular Biology, Experimental Teaching Center, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China.
- 6Minhang Hospital, Fudan University, Shanghai 201199, China.
Abstract
Therapeutic vaccination for chronic hepatitis B aims to restore HBV-specific T-cell immunity and contribute to a functional cure. We systematically compared the immune profiles and antiviral efficacy of four vaccine modalities: recombinant HBsAg (rHBsAg), antigen-antibody immune complex (IC), a DNA vaccine encoding HBsAg (DNA-HBsAg), and an HBsAg-Fc fusion DNA vaccine (DNA-HBsAg-Fc). In naïve mice, the rHBsAg vaccine predominantly induced anti-HBs IgG responses, whereas the IC vaccine elicited strong anti-HBs IgG and detectable CD4⁺ T-cell responses. In contrast, DNA vaccines preferentially induced HBsAg-specific CD8⁺ T-cell immunity, which was further enhanced by fusion to the Fc fragment of human IgG1. In the pre-immunization/AAV-HBV model, high anti-HBs titers in rHBsAg and IC groups were associated with rapid clearance of circulating HBsAg but not with comparable reductions in HBcAg⁺ hepatocytes, whereas stronger HBsAg-specific CD8⁺ T-cell responses in the DNA vaccine groups were associated with greater reductions in HBcAg⁺ hepatocytes. However, in the therapeutic AAV-HBV model, all vaccine monotherapies showed limited and non-sustained antiviral efficacy, with only transient reductions in serum HBsAg and limited reductions in HBcAg⁺ hepatocytes. These findings highlight the distinct immune profiles of different vaccine platforms and an association between stronger HBsAg-specific CD8⁺ T-cell responses and reduced intrahepatic HBcAg expression, while underscoring the limited efficacy of vaccine monotherapy in the AAV-HBV model.
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BibTeX
@article{xiao2026immune,
title = {{Immune Profiles Elicited by Different HBV Vaccine Modalities and Their Associations with Serological and Intrahepatic Viral Outcomes.}},
author = {Huiying Xiao and Jinhang He and Lili Zhu and Songmei Wang and Chao Qiu and Xuanyi Wang},
journal = {International journal of molecular sciences},
year = {2026},
month = sep,
doi = {10.3390/ijms27198499},
url = {https://europepmc.org/article/MED/42883747},
note = {CC BY},
}
RIS
TY - JOUR
TI - Immune Profiles Elicited by Different HBV Vaccine Modalities and Their Associations with Serological and Intrahepatic Viral Outcomes.
AU - Huiying Xiao
AU - Jinhang He
AU - Lili Zhu
AU - Songmei Wang
AU - Chao Qiu
AU - Xuanyi Wang
PY - 2026
DA - 2026/09/23
JO - International journal of molecular sciences
DO - 10.3390/ijms27198499
UR - https://europepmc.org/article/MED/42883747
AB - Therapeutic vaccination for chronic hepatitis B aims to restore HBV-specific T-cell immunity and contribute to a functional cure. We systematically compared the immune profiles and antiviral efficacy of four vaccine modalities: recombinant HBsAg (rHBsAg), antigen-antibody immune complex (IC), a DNA vaccine encoding HBsAg (DNA-HBsAg), and an HBsAg-Fc fusion DNA vaccine (DNA-HBsAg-Fc). In naïve mice, the rHBsAg vaccine predominantly induced anti-HBs IgG responses, whereas the IC vaccine elicited strong anti-HBs IgG and detectable CD4⁺ T-cell responses. In contrast, DNA vaccines preferentially induced HBsAg-specific CD8⁺ T-cell immunity, which was further enhanced by fusion to the Fc fragment of human IgG1. In the pre-immunization/AAV-HBV model, high anti-HBs titers in rHBsAg and IC groups were associated with rapid clearance of circulating HBsAg but not with comparable reductions in HBcAg⁺ hepatocytes, whereas stronger HBsAg-specific CD8⁺ T-cell responses in the DNA vaccine groups were associated with greater reductions in HBcAg⁺ hepatocytes. However, in the therapeutic AAV-HBV model, all vaccine monotherapies showed limited and non-sustained antiviral efficacy, with only transient reductions in serum HBsAg and limited reductions in HBcAg⁺ hepatocytes. These findings highlight the distinct immune profiles of different vaccine platforms and an association between stronger HBsAg-specific CD8⁺ T-cell responses and reduced intrahepatic HBcAg expression, while underscoring the limited efficacy of vaccine monotherapy in the AAV-HBV model.
SN - 1422-0067
ER -