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Activity and safety of DNA plasmids encoding IL-4 and IFN gamma

Gene Therapy volume 6, pages 237–244 (1999)Cite this article

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 IFNγ (pIFNγ) 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 pIFNγ 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 pIFNγ 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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Authors and Affiliations

  1. Division of Viral Products, Retroviral Immunology Section, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, 20892, MD, USA

    K J Ishii, M Ichino, D Verthelyi & D M Klinman

  2. Malaria Program Naval Medical Research Institute, Bethesda, 20889, MD, USA

    W R Weiss

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  1. K J Ishii
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  2. W R Weiss
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Ishii, K., Weiss, W., Ichino, M. et al. Activity and safety of DNA plasmids encoding IL-4 and IFN gamma. Gene Ther 6, 237–244 (1999). https://doi.org/10.1038/sj.gt.3300799

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