Humoral and cellular immunity to an encoded protein induced by direct DNA injection.
An immunization procedure with naked DNA that generates both humoral and cellular immune responses is described. A mammalian expression vector encoding human factor IX as an example of immunogen was injected into mice three times at 10-day intervals. Three of the 4 mice in which the DNA was injected intramuscularly and 5 of the 9 mice injected subcutaneously produced antibodies to human factor IX. Spleen cells from inoculated mice also showed significant cytotoxic T lymphocyte response to target cells expressing human factor IX. The titers of anti-single-stranded (ss)DNA antibodies were significantly higher in the subsets of genetically inoculated mice than in the control mice, but anti-double-stranded (ds)DNA antibodies were not detected in any serum samples. Thus, intramuscular and subcutaneous injection of plasmid DNA can induce immune responses against the encoded protein without an exposure to virus particles, and this approach may serve as the basis for immunotherapy in the treatment of cancer and infectious diseases in humans.
Katsumi
A
A
First Department of Internal Medicine, Nagoya University School of Medicine, Japan.
Emi
N
N
Abe
A
A
Hasegawa
Y
Y
Ito
M
M
Saito
H
H
D000818:Animals; D000974:Antibodies, Antinuclear / Q000096:biosynthesis; D000917:Antibody Formation; D004274:DNA, Recombinant / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology; D004277:DNA, Single-Stranded / Q000276:immunology; D005164:Factor IX / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D007111:Immunity, Cellular; D007273:Injections, Intramuscular; D007279:Injections, Subcutaneous; D007959:Lymphocyte Culture Test, Mixed; D051379:Mice; D008811:Mice, Inbred DBA; D008979:Moloney murine leukemia virus / Q000235:genetics; D010957:Plasmids / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000276:immunology*; D014162:Transfection / Q000379:methods*; D014407:Tumor Cells, Cultured
D000974:Antibodies, Antinuclear; D004274:DNA, Recombinant; D004277:DNA, Single-Stranded; D011993:Recombinant Fusion Proteins; D005164:Factor IX