Immunization with recombinant Calmette-Guerin bacillus (BCG)-hepatitis C virus (HCV) elicits HCV-specific cytotoxic T lymphocytes in mice.
Since virus-specific cytotoxic T lymphocytes (CTLs) play a critical role in preventing the spread of hepatitis C virus (HCV), an effective HCV vaccine should be capable of eliciting HCV-specific CTLs. In the present study, we assessed the capability of a novel recombinant vaccine using an attenuated tuberculosis bacillus, Calmette-Guerin bacillus (BCG), as a vaccine vehicle to elicit HCV-specific CTLs. BCG was engineered to express the CTL epitope of HCV-non-structure protein 5a (NS5a) as a chimeric protein with alpha antigen of mycobacteria. Immunization with this recombinant BCG elicited major histocompatibility complex class I-restricted CD8(+) HCV-NS5a-specific CTLs in mice. Immunized mice showed a substantial reduction in the vaccinia virus titer compared with control mice when the immunized mice were challenged with a recombinant vaccinia virus expressing HCV-NS5a genes. These findings provide evidences for the possibility of BCG as a vaccine vector and its continued exploration as a vehicle for eliciting HCV-specific immunity.
Uno-Furuta
Satori
S
Department of Bioregulation, Mie University School of Medicine, 2-174 Edobashi, Tsu, Mie, 514-8507, Japan.
Matsuo
Kazuhiro
K
Tamaki
Shigenori
S
Takamura
Shiki
S
Kamei
Akira
A
Kuromatsu
Isao
I
Kaito
Masahiko
M
Matsuura
Yoshiharu
Y
Miyamura
Tatsuo
T
Adachi
Yukihiko
Y
Yasutomi
Yasuhiro
Y
D000818:Animals; D001500:BCG Vaccine / Q000276:immunology*; D015153:Blotting, Western; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003001:Cloning, Molecular; D016207:Cytokines / Q000096:biosynthesis; D003601:Cytotoxicity Tests, Immunologic; D000939:Epitopes / Q000276:immunology; D005260:Female; D005805:Genes, MHC Class I / Q000276:immunology; D016174:Hepacivirus / Q000276:immunology*; D018937:Hepatitis C Antibodies / Q000096:biosynthesis* / Q000235:genetics; D007114:Immunization; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D009161:Mycobacterium / Q000276:immunology; D009841:Oligonucleotides / Q000276:immunology; D010455:Peptides / Q000138:chemical synthesis / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000276:immunology; D017361:Viral Nonstructural Proteins / Q000276:immunology; D012324:RNA-Dependent RNA Polymerase
D001500:BCG Vaccine; D016207:Cytokines; D000939:Epitopes; D018937:Hepatitis C Antibodies; D009841:Oligonucleotides; D010455:Peptides; D014614:Vaccines, Synthetic; D017361:Viral Nonstructural Proteins; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase