Intravascular naked DNA vaccine encoding glycoprotein B induces protective humoral and cellular immunity against herpes simplex virus type 1 infection in mice

Abstract

Naked plasmid DNA (pDNA) vaccine expressing herpes simplex virus type 1 (HSV-1) glycoprotein B (gB) was tested for protective activity against acute HSV-1 infection in mice. The pDNA was intravenously injected into Balb/c mice via their tail vein under high pressure, and the vaccination was performed two times at an interval of 7 days. The gB gene vaccination significantly protected the mice from subsequent intraperitoneal challenge with a lethal dose of HSV-1, which killed all the animals given control plasmid or saline. The protective activity was correlated with the dose of the plasmid inoculated, the survival rate reaching 83% in mice vaccinated with 5 mg of pDNA. The vaccinated mice were also protected from latent HSV infection. The immunized mice showed significant elevation in neutralizing antibody against HSV-1 as well as serum levels of interleukin-12 (IL-12) and interferon-g (IFN-g). When mice were immunized with 5 mg of an Epstein-Barr virus (EBV)-based plasmid vector harboring the gB, the cytotoxic T lymphocytes (CTLs) activity and proliferative response for HSV-1 were also induced. The results strongly suggest that intravenous immunization of naked pDNA may induce humoral and cellular immune responses against the virus, leading to a significant prophylactic outcome against HSV-1 infection in mice.

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

“…The intravascular immunization of 1 mg of the gB gene alone significantly elevated IL-12 and IFN-g concentrations in sera of mice, suggesting that a Th1 response can be triggered in the absence of exogenous IL-12 ( Figure 6 and our previous paper 13 ). The magnitude of the Th1 Figure 4a.…”

“…3,4,7,8 In our previous report, 5 mg of gB pDNA administered via an intravascular route allowed approximately 80% of mice to survive fatal HSV infection. 13 The present findings indicate that the coadministration of the IL-12 expression construct further reduced the dose of the vaccine that is required for induction of successful immune prevention. Indeed, 100% of mice escaped death by acute infection when 1 mg each of the vaccine and adjuvant plasmids was coinjected.…”

“…[10][11][12] As a result, the animals were highly resistant to a subsequent lethal HSV-1 challenge. 13 The surviving mice also escaped latent infection, which was not reported in earlier studies using intramuscular pDNA vaccination. The intravascular pDNA vaccine induced not only humoral but also CTL responses.…”

“…13 To examine whether coadministration with immunomodulatory cytokine genes further improved the prophylactic effect of the pDNA vaccine, mice were injected twice with 1 mg of pGEG.gB, singly or in combination with 1 mg of expression vector plasmid encoding IL-10, IL-12, IL-15, IL-18 or IL-21. Following systemic inoculation with a lethal dose of HSV-1, all the control mice that had been left untreated or sham-immunized with saline died by day 9 (Figure 1 (Figure 1b).…”

“…13 Mice coadministered with pGEG.gB and pGEG.mIL-12 showed strong cytotoxic activity against the gB-positive target cells (Figure 5a). The killing was revealed to be specific for the gB antigen, because the same effector cells failed to show any cytotoxicity against parental P815 cells lacking the viral antigen ( Figure 5b).…”