Induction of cytotoxic T lymphocytes and antitumor immunity with DNA vaccines expressing single T cell epitopes.
Delivery of genetic expression constructs into living animals can effectively induce both humoral and cellular immunity to the expressed proteins. Here we test the effectiveness of genetic immunization with a minigene coding for single epitopes derived from mutant p53 or from HIV gp120. We show that when these constructs are delivered by particle bombardment-mediated DNA transfer into the skin of mice, it results in efficient induction of tumor protective CTL. The immunogenicity of the epitope derived from mutant p53 is significantly enhanced if the epitope sequence is fused in frame with the adenovirus E3 leader sequence to target the epitope to the endoplasmic reticulum, thus acting like a "genetic adjuvant." We conclude that genetic T cell epitope immunization is an alternative to peptide-based techniques for eliciting an effective immune response targeted against a single defined epitope. in some cases, the fusion of the gene product of the DNA vaccine vector with an endoplasmic reticulum targeting sequence may enhance immune induction.
Ciernik
I F
IF
Simmons Cancer Center, University of Texas, Southwestern Medical Center, Dallas, TX 75235, USA.
Berzofsky
J A
JA
Carbone
D P
DP
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D001483:Base Sequence; D004247:DNA / Q000235:genetics* / Q000276:immunology*; D004721:Endoplasmic Reticulum / Q000276:immunology; D000939:Epitopes / Q000235:genetics; D005260:Female; D016158:Genes, p53; D015699:HIV Envelope Protein gp120 / Q000235:genetics; D006801:Humans; D007114:Immunization; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009374:Neoplasms, Experimental / Q000276:immunology* / Q000517:prevention & control; D009838:Oligodeoxyribonucleotides / Q000235:genetics; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000235:genetics / Q000494:pharmacology*
D000939:Epitopes; D015699:HIV Envelope Protein gp120; D009838:Oligodeoxyribonucleotides; D014614:Vaccines, Synthetic; D004247:DNA