Identification of novel hepatitis B virus therapeutic vaccine candidates derived from polymerase protein
| Autor: | Jinming Wu, Yilun Xu, Juzeng Zheng, Yang Liu, Xianfan Lin, Ziqiang Xia, Sisi Jin, Zhanfan Ou |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Gene Expression Regulation
Viral Hepatitis B virus Aging Peptide binding DNA-Directed DNA Polymerase Biology medicine.disease_cause Peripheral blood mononuclear cell Fluorescence Epitope Epitopes Interferon-gamma Viral Proteins Immune system Cell Line Tumor vaccine Gene expression medicine Humans Amino Acid Sequence Polymerase epitope Cell Death Viral Vaccines bioinformatics Cell Biology Virology digestive system diseases Molecular Docking Simulation polymerase Viral replication biology.protein Peptides Protein Binding Research Paper |
| Zdroj: | Aging (Albany NY) |
| ISSN: | 1945-4589 |
| DOI: | 10.18632/aging.203053 |
| Popis: | Hepatitis B virus (HBV) infection is a worldwide health problem with high morbidity and mortality rates. The therapeutic vaccine is a promising method of treatment, and HBV polymerase plays a vital role in viral replication. Therefore, a therapeutic vaccine that binds to HBV DNA polymerase may control HBV infection. We predicted and selected epitopes of polymerase using online databases and analysis software. We then performed molecular docking and peptide binding assays to evaluate the binding energies and affinities between polymerase epitopes and the HLA-A0201 molecule. Finally, we induced T cells from the peripheral blood mononuclear cells (PBMCs) of healthy donors using each epitope and quantified the functions of epitope-specific T cells by IFN-γELISPOT assay, T2 cell cytotoxicity assay, HepG2.2.15 cell cytotoxicity assay and HBV gene expression assays. Four epitopes (RVTGGVFLV, GLLGFAAPF, LLDDEAGPL and YMDDVVLGA) had low binding energy and two epitopes (RVTGGVFLV and GLLGFAAPF) had a high binding affinity. The T cells stimulated by two epitopes (GLLGFAAPF and HLYSHPIIL) had a greater ability to induce immune response and suppress HBV. The HBV DNA polymerase epitopes identified in this study are promising targets for designing an epitope-based therapeutic vaccine against HBV. |
| Databáze: | OpenAIRE |
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