Enhancement of DNA vaccine potency against herpes simplex virus 1 by co-administration of an interleukin-18 expression plasmid as a genetic adjuvant.

Department of Pharmacology, Beijing Institute of Ophthalmology, Beijing 100062, PR ChinaIn this study, the immune-modulatory and vaccine effects of using an interleukin (IL)-18 expressionplasmid as a genetic adjuvant to enhance DNA vaccine-induced immune responses wereinvestigated in a mouse herpes simplex virus 1 (HSV-1) challenge model. BALB/c mice wereimmunized by three intramuscular inoculations ofHSV-1 glycoprotein D(gD) DNAvaccine alone orin combination with a plasmid expressing mature IL-18 peptide. Both the serum IgG2a/IgG1 ratioand T helper 1-type (Th1) cytokines [IL-2 and interferon (IFN)-a] were increased significantly by theco-injection of the IL-18 plasmid compared with the injection of gD DNA alone. However, theproduction of IL-10 was inhibited by IL-18 plasmid co-injection. Furthermore, IL-18 plasmid co-injection efficiently enhanced antigen-specific lymphocyte proliferation and the delayed-typehypersensitivityresponse.WhenmicewerechallengedwithHSV-1atthecornea,co-injectionofIL-18 plasmid with gD DNA vaccine showed significantly better protection, manifested as lowercorneal lesion scores and faster recovery. These experiments indicate that co-injection of an IL-18plasmid with gD DNA vaccine efficiently induces Th1-dominant immune responses and improvesthe protective effect against HSV-1 infection.