Protection against a lethal challenge with SV40-transformed cells by the direct injection of DNA-encoding SV40 large tumor antigen.
Plasmid DNA encoding the large tumor antigen (T- ag) of SV40 was used to actively immunize mice to assess the induction of SV40 T-ag-specific immunity. Mice were injected with the naked DNA i.m., and immune responses were compared to those elicited in mice immunized with the recombinant SV40 T-ag protein. Compared to immunization with the recombinant protein, naked DNA induced weak antibody responses to SV40 T-ag. No increase in natural killer cell activity was observed following either recombinant protein or nucleic acid vaccination. However, the recombinant SV40 T-ag failed to induce SV40 T-ag-specific CTL responses, whereas the plasmid DNA encoding SV40 T-ag elicited CTL activity specific for SV40 T-ag. The SV40 T-ag-specific CTL lysed in vitro only syngeneic target cells (H-2(d)) expressing SV40 T-ag, indicating that the CTL are MHC restricted. Both the recombinant protein and naked DNA preparations induced immune responses that were protective against a lethal challenge with syngeneic SV40-transformed cells. A comparison of recombinant protein versus nucleic acid immunization indicates that both humoral and cell-mediated immune responses may play a role in SV40 T-ag immunity. These data indicate that active immunization with genes encoding tumor-specific antigens may be an efficacious strategy for the induction of tumor immunity.
Bright
R K
RK
Department of Virology and Immunology, Southwest Foundation for Biomedical Research, San Antonio, Texas 78228, USA.
Beames
B
B
Shearer
M H
MH
Kennedy
R C
RC
D000818:Animals; D000951:Antigens, Neoplasm / Q000235:genetics / Q000276:immunology*; D002461:Cell Line, Transformed; D002472:Cell Transformation, Viral; D017690:Cell Transplantation; D004279:DNA, Viral / Q000008:administration & dosage / Q000276:immunology*; D007109:Immunity; D051379:Mice; D008807:Mice, Inbred BALB C; D013539:Simian virus 40 / Q000276:immunology*
D000951:Antigens, Neoplasm; D004279:DNA, Viral