Cytokine genetic adjuvant facilitates prophylactic intravascular DNA vaccine against acute and latent herpes simplex virus infection in mice

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

IL-21 Administration into the Nostril Alleviates Murine Allergic Rhinitis

“…They were purified using Qiagen Maxi Prep EndoFree kits (Qiagen). The in vivo gene transfer was performed as described (17). Briefly, BALB/c mice were i.v.…”

“…IL-21 exerts pleiotropic activities on a variety of target cells, alone or in combination with other cytokines (10,11). Several studies have indicated that IL-21 regulates the differentiation, growth, and activation of Th1 (9,(11)(12)(13), Th2 (14), and CTL (15)(16)(17) as well as NK cells (11), whereas myeloid cells, including dendritic cells (18,19) and macrophages (14,20), are also stimulated by this cytokine (21).…”

Increased Level and Longevity of Protective Immune Responses Induced by DNA Vaccine Expressing the HIV-1 Env Glycoprotein when Combined withIL-21andIL-15Gene Delivery

“…In view of these findings, it has been suggested that IL-21 can influence both innate and adaptive immunity (43,45). In fact, IL-21 has recently been shown to increase survival rates of HSV-1-infected mice when coinjected with a plasmid DNA encoding HSV-1 glycoprotein B Ag (47), and mice treated with IL-21 have been able to reject tumor cells and develop tumor-specific immune responses (40, 48 -50).…”

DNA Vaccines against Infectious Diseases and Cancer

“…In simian immunodeficiency virus (SIV)-infected macaques, furthermore, codelivery of SIV DNA vaccines plus IL-12 or IL-15 cDNA improved Ag-specific CD8+ effector memory T cell responses (Halwani et al, 2008). Another Th1 type cytokine, IL-21 was also demonstrated to be effective as equally as IL-12, IL-15, and IL-18 for augmenting HSV-1 gB-based DNA vaccine potency (Cui et al, 2005). More recently, EP delivery of IL-12 cDNA showed a similar result.…”