Effect of the hepatitis B virus S-ecdCD40L vaccine therapy in HBV transgenic mice: A vaccine-induced activation of antigen presenting dendritic cells
| Autor: | Binbin Tang, Songsong Lan, Yin Xu, Huaqin Guan, Jinming Wu |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Hepatitis B virus Cancer Research HBsAg medicine.medical_treatment Antigen-Presenting Cells Mice Transgenic Biology Lymphocyte Activation medicine.disease_cause Biochemistry DNA vaccination Mice 03 medical and health sciences 0302 clinical medicine Antigen Vaccines DNA Genetics medicine Animals Hepatitis B Vaccines Molecular Biology Inflammation Mice Inbred BALB C Hepatitis B Surface Antigens CD40 Vaccination Immunotherapy Active virus diseases Dendritic Cells Immunotherapy Hepatitis B Vaccine efficacy Interleukin-12 Virology digestive system diseases Vaccine therapy 030104 developmental biology Liver Oncology Immunology biology.protein Molecular Medicine Immunization 030215 immunology |
| Zdroj: | Molecular Medicine Reports. 16:6102-6108 |
| ISSN: | 1791-3004 1791-2997 |
| DOI: | 10.3892/mmr.2017.7322 |
| Popis: | The classical hepatitis B virus (HBV) DNA vaccination plasmid only encodes for a single viral antigen, either the S or the PreS2/S antigen. Many strategies have been employed to improve the effect of these DNA vaccines. Our previous study identified that the fusion gene, HBV S‑ecd cluster of differentiation 40 ligand (CD40L), may promote the activation of dendritic cells (DCs) and enhance their function in vitro. In the current study, the effect of HBV S‑ecdCD40L vaccine therapy on liver DCs was investigated, and its therapeutic potential in HBV transgenic (HBV‑Tg) mice was evaluated. The eukaryotic expression plasmid, pcDNA3.1‑S‑ecdCD40L, was constructed by inserting the HBV S gene and mouse CD40L gene into the vector, pcDNA3.1 (+). HBV‑Tg mice were immunized with pcDNA3.1‑S‑ecdCD40L, pcDNA3.1‑S, pcDNA3.1 or PBS. Following this, immunophenotyping, cytokine production and T‑cell activation were analyzed in the CD11c‑enriched DC population obtained from the liver. Vaccine efficacy was further assessed by the detection of serological and biochemical parameters. When comparing with other control groups, DCs from HBV‑Tg mice immunized with pcDNA3.1‑S‑ecdCD40L exhibited increased expression of immunologically important cell molecules (CD86 and major histocompatibility complex class II), pro‑inflammatory cytokines (interleukin‑12), and enhanced capacity to promote allogeneic T‑cell proliferation. Furthermore, the HBV S‑ecdCD40L vaccine resulted in a significant inhibition of HBV DNA replication and downregulation of the hepatitis B virus surface antigen (HBsAg) in HBV‑Tg mice, without obvious liver injury. In conclusion, the HBV S‑ecdCD40L vaccine may be a feasible strategy for chronic HBV immunotherapy via promoting DC activation and function. |
| Databáze: | OpenAIRE |
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