Modulation of Immune Responses to DNA Vaccines by Coexpression of Cytokine Genes

Mi-Hua Tao

《Journal of Genetics and Molecular Biology》 13卷1期 (2002/03) Pp. 62-62

https://doi.org/10.30047/JGMB.200203.0018

並列摘要

DNA vaccines containing genes for an antigenic portion of a variety of pathogens have recently been developed as a novel vaccination technology. The magnitude and nature of these immune responses to DNA vaccines can be further manipulated by codelivery of cytokine genes. The IL-12 gene was reported to polarize the immune responses to DNA vaccines toward Th1 development, stimulate strong CTL activity, and increase protective immunity. However, in this study, we show that co-administration of a IL-12-expressing plasmid (pIL-12) significantly suppressed the protective immunity elicited by a plasmid DNA vaccine (pE) encoding the envelope protein of Japanese encephalitis virus (JEV). This suppressive effect was associated with marked reduction of specific T-cell proliferation and antibody responses. A single dose of PIL-12 treatment with plasmid pE in initial priming resulted in significant immune suppression to subsequent pE booster immunization. The pIL-12-mediated immune suppression was dose dependent and evident only when the IL-12 gene was injected either before or coincident with the pE DNA vaccine. Finally, using IFN –γ gene-disrupted mice we showed that the suppressive activity of the IL-12 plasmid was dependent upon endogenous production of IFN-γ. These results demonstrate that coexpression of the IL-12 gene can sometimes produce untoward effects to immune responses and thus its application as a vaccine adjuvant should be carefully evaluated.