Activity and safety of DNA plasmids encoding IL-4 and IFN gamma.
Gene Ther
; 6(2): 237-44, 1999 Feb.
Article
in En
| MEDLINE
| ID: mdl-10435108
ABSTRACT
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.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Plasmids
/
Genetic Therapy
/
Adjuvants, Immunologic
/
Interleukin-4
/
Interferon-gamma
/
Vaccines, DNA
Limits:
Animals
Language:
En
Journal:
Gene Ther
Journal subject:
GENETICA MEDICA
/
TERAPEUTICA
Year:
1999
Document type:
Article
Affiliation country:
United States