Activity and safety of DNA plasmids encoding IL-4 and IFN gamma.
Cytokine-encoding DNA plasmids can act as 'genetic adjuvants', improving the immune response stimulated by co-administered DNA vaccines. We examined whether plasmids encoding the Th1 cytokine IFN gamma (pIFN gamma) or the Th2 cytokine IL-4 (pIL-4) have long-term effects on immune homeostasis when administered to adult mice, or alter immune maturation in neonates. Both plasmids boosted immunity against a co-administered vaccine, with pIFN gamma promoting the development of a Th1 response (characterized by the production of IgG2a antibodies), and pIL-4 preferentially stimulating a Th2 response (characterized by increased IgG1 antibody production). Both pIFN gamma and pIL-4 influenced the ratio of cells actively secreting Th1 versus Th2 cytokines, consistent with an effect on Th cell maturation. Interestingly, this effect persisted for only a few weeks and was not magnified by repeated plasmid administration. Cytokine-encoding plasmids had no long-term effect on the immune response of newborn or adult mice to subsequent antigenic stimulation, nor did they selectively induce the production of pathogenic anti-DNA autoantibodies. These results suggest cytokine-encoding plasmids may be safe as immune adjuvants.
Ishii
K J
KJ
Retroviral Immunology Section, Food and Drug Administration, Bethesda, MD 20892, USA.
Weiss
W R
WR
Ichino
M
M
Verthelyi
D
D
Klinman
D M
DM
D000276:Adjuvants, Immunologic; D000818:Animals; D000831:Animals, Newborn; D000906:Antibodies / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D015316:Genetic Therapy / Q000379:methods*; D007074:Immunoglobulin G; D007371:Interferon-gamma / Q000235:genetics*; D015847:Interleukin-4 / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D010957:Plasmids / Q000008:administration & dosage*; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D019444:Vaccines, DNA / Q000008:administration & dosage*
D000276:Adjuvants, Immunologic; D000906:Antibodies; D007074:Immunoglobulin G; D019444:Vaccines, DNA; D015847:Interleukin-4; D007371:Interferon-gamma