Protection of Novel Adenovirus Vectored Vaccine in Rats Against Wild-Type Hepacivirus and Variant Infections
This article relates to:
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Optimising Adenovirus-Vectored Vaccines for Hepacivirus: Immunity Gaps and Future Directions
- Volume 45Issue 5Liver International
- First Published online: April 16, 2025
Shengxue Luo
Institute of Clinical Blood Transfusion, Guangzhou Blood Center, Guangzhou, China
Search for more papers by this authorQitao Deng
Department of Transfusion Medicine, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, China
Search for more papers by this authorChaolan Liang
Department of Blood Transfusion, Shenzhen Third People's Hospital, Shenzhen, China
Search for more papers by this authorPanli Zhang
Department of Transfusion Medicine, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, China
Guangzhou Bai Rui Kang (BRK) Biological Science and Technology Limited Company, Guangzhou, China
Search for more papers by this authorPeng Zou
Department of Transfusion Medicine, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, China
Search for more papers by this authorShikai Deng
Department of Transfusion Medicine, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, China
Search for more papers by this authorMeng Zhang
Department of Thyroid and Breast Surgery, Shenzhen Hospital of Southern Medical University, Shenzhen, Guangdong, China
Search for more papers by this authorFeifeng Zeng
Institute of Clinical Blood Transfusion, Guangzhou Blood Center, Guangzhou, China
Institute of Blood Transfusion and Hematology, Guangzhou Blood Center, Guangzhou Medical University, Guangzhou, China
Search for more papers by this authorLing Zhang
Department of Transfusion Medicine, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, China
Search for more papers by this authorCorresponding Author
Yongshui Fu
Institute of Clinical Blood Transfusion, Guangzhou Blood Center, Guangzhou, China
Department of Transfusion Medicine, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, China
Institute of Blood Transfusion and Hematology, Guangzhou Blood Center, Guangzhou Medical University, Guangzhou, China
Correspondence:
Yongshui Fu ([email protected])
Chengyao Li ([email protected])
Tingting Li ([email protected])
Search for more papers by this authorCorresponding Author
Chengyao Li
Department of Transfusion Medicine, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, China
Correspondence:
Yongshui Fu ([email protected])
Chengyao Li ([email protected])
Tingting Li ([email protected])
Search for more papers by this authorCorresponding Author
Tingting Li
Department of Transfusion Medicine, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, China
Shenzhen Bao'an District Central Blood Station, Shenzhen, People's Republic of China
Correspondence:
Yongshui Fu ([email protected])
Chengyao Li ([email protected])
Tingting Li ([email protected])
Search for more papers by this authorShengxue Luo
Institute of Clinical Blood Transfusion, Guangzhou Blood Center, Guangzhou, China
Search for more papers by this authorQitao Deng
Department of Transfusion Medicine, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, China
Search for more papers by this authorChaolan Liang
Department of Blood Transfusion, Shenzhen Third People's Hospital, Shenzhen, China
Search for more papers by this authorPanli Zhang
Department of Transfusion Medicine, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, China
Guangzhou Bai Rui Kang (BRK) Biological Science and Technology Limited Company, Guangzhou, China
Search for more papers by this authorPeng Zou
Department of Transfusion Medicine, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, China
Search for more papers by this authorShikai Deng
Department of Transfusion Medicine, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, China
Search for more papers by this authorMeng Zhang
Department of Thyroid and Breast Surgery, Shenzhen Hospital of Southern Medical University, Shenzhen, Guangdong, China
Search for more papers by this authorFeifeng Zeng
Institute of Clinical Blood Transfusion, Guangzhou Blood Center, Guangzhou, China
Institute of Blood Transfusion and Hematology, Guangzhou Blood Center, Guangzhou Medical University, Guangzhou, China
Search for more papers by this authorLing Zhang
Department of Transfusion Medicine, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, China
Search for more papers by this authorCorresponding Author
Yongshui Fu
Institute of Clinical Blood Transfusion, Guangzhou Blood Center, Guangzhou, China
Department of Transfusion Medicine, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, China
Institute of Blood Transfusion and Hematology, Guangzhou Blood Center, Guangzhou Medical University, Guangzhou, China
Correspondence:
Yongshui Fu ([email protected])
Chengyao Li ([email protected])
Tingting Li ([email protected])
Search for more papers by this authorCorresponding Author
Chengyao Li
Department of Transfusion Medicine, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, China
Correspondence:
Yongshui Fu ([email protected])
Chengyao Li ([email protected])
Tingting Li ([email protected])
Search for more papers by this authorCorresponding Author
Tingting Li
Department of Transfusion Medicine, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, China
Shenzhen Bao'an District Central Blood Station, Shenzhen, People's Republic of China
Correspondence:
Yongshui Fu ([email protected])
Chengyao Li ([email protected])
Tingting Li ([email protected])
Search for more papers by this authorHandling Editor: Luca Valenti
Funding: This work was supported by the National Natural Science Foundation of China (nos 32070929, 82 271868, 32471001 and 82302001), Guangdong Natural Science Foundation Outstanding Youth Project (2022B1515020050), Guangdong Basic and Applied Basic Research Foundation (2021A1515110991, 2021A1515110963 and 2024A1515011469), Science and Technology Projects in Guangzhou (2023A03J0552, 2024A03J0079, 2024A04J6607 and 2025A04J3392).
Shengxue Luo, Qitao Deng, and Chaolan Liang contributed equally to this work.
ABSTRACT
Background and Aims
Hepatitis C virus (HCV) vaccines are urgently needed to achieve WHO's goal for the elimination of viral hepatitis by 2030. The lack of suitable animal models for evaluating vaccine efficacy has greatly hindered the development of HCV vaccines. By using the rat model chronically infected with rodent hepacivirus from Rattus norvegicus (RHV-rn1), a hepacivirus homologously close to HCV as a surrogate model of HCV infection, we assessed the protective effectiveness of the RHV-rn1 vaccine Sad23L-RHVns.
Methods
Sad23L-RHVns vaccine was constructed with the nonstructural proteins (NS) 3–5B genes of RHV-rn1. SD rats were immunised with Sad23L-RHVns by prime or prime-boost regimen via intramuscular injection, then challenged 4 weeks post vaccination by RHV-rn1. A part of the rats were rechallenged with a variant 15 weeks post the first challenge of RHV-rn1.
Results
The specific T-cell responses to NS3-5B antigens were induced by prime immunisation, which were significantly enhanced by boost vaccination. The inoculated rats and controls were challenged by wild-type RHV-rn1, of all the primed and control rats having persistently high levels of viremia, whereas 7 of 9 (77.8%) boosted rats cleared RHV-rn1 infection. Interestingly, the resolver acquired immune protection against re-challenging with variant and showed significantly higher T-cell responses than the nonresolver in 25 weeks post rechallenge.
Conclusions
Sad23L-RHVns with prime-boost regimen protected 77.8% of rats against wild-type RHV-rn1 infection, and resolvers showed high levels and maintenance of T cell immunity against the variant. Our findings that maintenance of effective T cell immunity is required for RHV-rn1 resolution may provide insight to develop the HCV vaccine in humans.
Conflicts of Interest
The authors declare no conflicts of interest.
Open Research
Data Availability Statement
All data generated or analysed during this study are included in this published article (and its Supporting Information).
Supporting Information
| Filename | Description |
|---|---|
| liv70045-sup-0001-supinfo.pdfPDF document, 1.3 MB |
Data S1. |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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Citing Literature
