Strong augment effect of IL-12 expression plasmid on the induction of HIV-specific cytotoxic T lymphocyte activity by a peptide vaccine candidate.
We previously reported that repeated inoculation of VC1, a macromolecular multicomponent peptide vaccine emulsified with Freund's adjuvant (VC1-F), induced high cytotoxic T lymphocyte (CTL) levels and a substantial level of multivalent antibodies which neutralized various human immunodeficiency virus type 1 (HIV-1) isolates. In the present study, we report that inoculation of VC1-F plus interleukin (IL)-12 expression plasmid can induce a higher antigen-specific CTL response compared to that with VC1-F alone. VC1-F plus IL-12 expression plasmid or VC1-F alone were inoculated to BALB/c mice twice at interval of 2 weeks. Two weeks after the second inoculation, spleen effector cells from these mice were examined. Stronger CTL responses against target cells were observed from the inoculation of VC1-F plus IL-12 plasmid than from that with VC-1F alone, but there was no difference in antibody induction. The inoculation of VC1 plus IL-12 plasmid also produced higher CTL activity than the inoculation of VC1 alone. These augmented CTL activities were not observed using target cells pulsed with non-HIV-specific peptides and different class I haplotype cells. These data demonstrate that co-inoculation of cell-mediated immune potent antigen and IL-12 plasmids can enhance the antigen-specific CTL response. This may be a potential approach for the induction of cellular immunization against HIV-1 and other diseases.
Hamajima
K
K
Department of Bacteriology, Yokohama City University School of Medicine, Japan.
Fukushima
J
J
Bukawa
H
H
Kaneko
T
T
Tsuji
T
T
Asakura
Y
Y
Sasaki
S
S
Xin
K Q
KQ
Okuda
K
K
D016915:AIDS Vaccines / Q000276:immunology*; D000276:Adjuvants, Immunologic / Q000096:biosynthesis; D000818:Animals; D000917:Antibody Formation; D005260:Female; D006678:HIV / Q000276:immunology*; D018664:Interleukin-12 / Q000096:biosynthesis*; D051379:Mice; D008807:Mice, Inbred BALB C; D010957:Plasmids / Q000378:metabolism*; D013602:T-Lymphocytes, Cytotoxic / Q000821:virology*; D017778:Vaccines, Combined / Q000494:pharmacology
D016915:AIDS Vaccines; D000276:Adjuvants, Immunologic; D017778:Vaccines, Combined; D018664:Interleukin-12