1. ¹Department of Microbiology, Kyoto Prefectural University of Medicine, Kyoto, Japan
2. ²Department of Microbiology and Immunology, Yanbian University College of Medicine, Yanji, China
3. ³Department of Internal Medicine, Affiliated Hospital of Yanbian University College of Medicine, Yanji, China
4. ⁴Division of Gastroenterology and Hepatology, Department of Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan

Correspondence: Dr O Mazda, Department of Microbiology, Kyoto Prefectural University of Medicine, Kamikyo, Kyoto 602-8566, Japan

Received 2 February 2004; Accepted 12 July 2004; Published online 7 October 2004.

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 g 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 g, all mice coadministered with 1 g 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-. 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.