Abstract
Intravascular plasmid DNA (pDNA) vaccine encoding herpes simplex virus type 1 (HSV-1) glycoprotein B (gB) effectively induces prophylactic immunity against lethal HSV-1 infection in mice. We investigated whether the vaccine potency is further improved by coadministration of cytokine genes together with a low dose of genetic vaccine. pDNA encoding IL-12, IL-15, IL-18 or IL-21 was capable of elevating survival rates of HSV-1-infected mice when coinjected with 1 μg of gB pDNA, while IL-10 gene delivery failed to affect the effectiveness of the genetic immunization. Although only 17% of mice survived acute HSV infection after the gB pDNA vaccination at a dose of 1 μg, all mice coadministered with 1 μg each of gB and IL-12 pDNAs not only survived the acute infection but also escaped latent infection. In these animals, the neutralizing antibody against HSV-1 was abundantly produced, and CTL activity against the gB antigen was augmented. Coadministration of the gB and IL-12 genes also elevated the serum level of interferon-γ. Adaptive transfer experiments indicated that soluble factors contributed to preventive immunity, while cell components alone were not capable of protecting mice from fatal viral infection. These results strongly suggest potential usefulness of Th1 cytokine genes as effective molecular adjuvants that facilitate specific humoral as well as cellular immune responses elicited by intravascular molecular vaccination.
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Acknowledgements
The present study was supported by a grant in aid from the Japanese Ministry of Education, Culture, Sports, Science and Technology. The bicistronic mIL-12 gene expression cassette and mouse IL-18 cDNA were generous gifts from Dr H Tahara (the Institute of Medical Science, University of Tokyo, Tokyo, Japan), and mouse IL-10 cDNA was kindly provided by Dr KW Moore (DNAX Research Institute, CA, USA). We also thank Dr WTV Germeraad (Academic Hospital Maastricht, Maastricht, the Netherlands) for critical reading of the manuscript.
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Cui, FD., Asada, H., Jin, ML. et al. Cytokine genetic adjuvant facilitates prophylactic intravascular DNA vaccine against acute and latent herpes simplex virus infection in mice. Gene Ther 12, 160–168 (2005). https://doi.org/10.1038/sj.gt.3302393
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DOI: https://doi.org/10.1038/sj.gt.3302393
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