RRC ID 54000
Author Yamamiya D, Mizukoshi E, Kaji K, Terashima T, Kitahara M, Yamashita T, Arai K, Fushimi K, Honda M, Kaneko S.
Title Immune responses of human T lymphocytes to novel hepatitis B virus-derived peptides.
Journal PLoS One
Abstract BACKGROUND & AIMS:Many individuals are infected with hepatitis B virus (HBV) worldwide, and this virus is commonly controlled by treatments with interferon (IFN)-alpha and nucleoside analogues (NA). However, the complete elimination of HBV by these treatments is difficult and, thus, the development of new treatments is needed. Host immune responses are closely involved in the elimination of HBV, suggesting the usefulness of immunotherapy. In the present study, we attempted to identify novel cytotoxic T-lymphocyte (CTL) epitopes that are useful for immunotherapy against HBV.
METHODS:CTL epitopes were predicted using computer software. Immune responses to each peptide were evaluated by IFN-γ ELISPOT and cytotoxic assays. The relationships between the immune responses to these newly identified CTL epitopes and the clinical backgrounds of patients and administration of NA were analyzed. Peptides were administered to mice as vaccines and peptide-specific T-cell induction was measured in vivo.
RESULTS:Positive reactions to 10 synthesized peptides were detected in 3 or more patients using the IFN-γ ELISPOT assay, and concentration-dependent cytotoxicity against 2 of these peptides was observed in the cytotoxic assay. Some peptides that correlated with serum ALT, HBsAg, and HBV core-related antigen (HBcrAg) levels were identified. Immune reactions against some peptides were enhanced by the administration of NA. Regarding their effects as a vaccine, peptide-specific T-cells were induced by four peptides in vivo.
CONCLUSIONS:Novel HBV epitopes that correlated with HBsAg and HBcrAg levels were identified. These newly identified epitopes may be useful in the analysis of immune responses to HBV and development of immunotherapy against HBV.
Volume 13(6)
Pages e0198264
Published 2018-6-1
DOI 10.1371/journal.pone.0198264
PII PONE-D-18-04543
PMID 29856876
PMC PMC5983448
MeSH Adult Aged Aged, 80 and over Animals Female Hep G2 Cells Hepatitis B / blood Hepatitis B / immunology* Hepatitis B Core Antigens / immunology Hepatitis B Surface Antigens / immunology Hepatitis B virus / immunology* Humans K562 Cells Male Mice Mice, Transgenic Middle Aged Peptides / immunology* T-Lymphocytes / immunology* T-Lymphocytes / virology*
IF 2.74
Times Cited 2
Human and Animal Cells Hep G2(RCB1886)