Recombinant polioviruses expressing hepatitis B virus-specific cytotoxic T-lymphocyte epitopes.
T-cell immune response to recombinant poliovirus expressing foreign antigens has not been elucidated well. In order to investigate the potential use of poliovirus as a T-cell vaccine vector, we constructed recombinant polioviruses expressing HBV-derived CTL epitopes, HBsAg(28-39) (L(d)-restricted; IPQSLDSWWTSL) and HBc(93-100) (K(b)-restricted; MGLKFRQL) at the junction between the P2 and P3 regions, designated V3CDs and V3CDc, respectively. The V3CDs and V3CDc recombinant viruses replicated efficiently in HeLa cells and showed a similar infection profile to that of the wild-type Mahoney strain in one-step growth kinetics. Genetic stability analysis showed that V3CDc retained the foreign insert over twelve successive passages examined, whereas V3CDs lost part of the foreign insert after four passages. Our results indicated that the stability of the inserted foreign sequences was rather affected by their nucleotide sequence than by their length when located between the P2 and P3 regions. The junction between these nonstructural protein-coding regions is a novel site for the construction of replication-competent recombinant poliovirus. Immunization of BALB/c (H-2(d)) and C57BL/6 mice (H-2(b)) with V3CDs and V3CDc, respectively, elicited significant antigen-specific CTL responses to HBsAg(28-39) but not to HBcAg(93-100).
Cho
S P
SP
Therapeutic Agent Center, Mogam Biotechnology Research Institute, Kyunggi-Do, South Korea.
Lee
B
B
Min
M K
MK
D000595:Amino Acid Sequence; D000818:Animals; D003602:Cytotoxicity, Immunologic / Q000235:genetics; D018984:Epitopes, T-Lymphocyte / Q000096:biosynthesis* / Q000235:genetics*; D005822:Genetic Vectors / Q000138:chemical synthesis / Q000276:immunology; D006367:HeLa Cells; D006515:Hepatitis B virus / Q000235:genetics* / Q000276:immunology*; D006801:Humans; D007700:Kinetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D017955:Poliovirus / Q000235:genetics* / Q000276:immunology*; D011995:Recombination, Genetic / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000821:virology*; D014162:Transfection; D014407:Tumor Cells, Cultured
D018984:Epitopes, T-Lymphocyte