The efficacy of a DNA vaccine encoding herpes simplex virus type 1 (HSV-1) glycoprotein D in decreasing ocular disease severity following corneal HSV-1 challenge

Abstract

Antiviral effects of a DNA vaccine against herpes simplex virus 1 (HSV-1) glycoprotein D (gD) were evaluated in eight week-old female BALB/c mice. The nuclease-insensitive construct (gD-ASOR) consisted of an HSV-1 gD encoding plasmid coupled to asialo orosomucoid (ASOR), targeting it to cells bearing ASOR receptors. Mice were immunized on day 0 and 7 with 10 microg doses of gD-ASOR or control substances. Fourteen days later, mice were infected by the corneal route with 10(5) pfu or 10(6) pfu HSV-1, strain 17syn+. Immunized mice showed a significant decrease in ocular disease severity over a 21-day observation period following infection compared to sham-immunized mice. Acute replication kinetic assays demonstrated a 100-fold decrease in viral titers on day 6 in trigeminal ganglia from immunized BALB/c mice compared to sham-immunized mice. Immunized mice showed a significant increase in numbers of CD4(+)T cells infiltrating the trigeminal ganglia at day 6 post infection compared to sham-immunized mice. Significant differences were not seen in latent viral reservoir between immunized and unimmunized mouse groups. Immunization with gD-ASOR decreased the severity of acute ocular HSV-1 infection, induced a CD4(+) T cell response, decreased the viral load in the trigeminal ganglia, but did not diminish viral latency.

Current developments in viral DNA vaccines: shall they solve the unsolved?

“…When expressed in the liver, it promoted a significant CTL cell response [75,76]. The ability of the above mentioned gD DNA vaccine to decrease ocular disease confirmed the benefits of the gD-ASOR construct, which enters any cells bearing ASOR receptors [77]. The ASORlinked DNA vaccination significantly increased the numbers of CD4/T cells along with the CD8/ T cell (CTL) response.…”

Prophylactic Vaccine Strategies and the Potential of Therapeutic Vaccines Against Herpes Simplex Virus

“…Development of HSV-1 DNA vaccines has focused on expressing gB [165,166] and gD [167], although other proteins have been studied to a lesser extent [29,168,169]. HSV-2 DNA vaccines expressing gB [170] or gD [170][171][172][173] alone, in combination [170], or with cytokines, elicit protective immunity in animal models, but none of these vaccines is yet licensed for human use.…”

Herpes simplex virus type 1 morphogenesis and virus‐cell interactions: significance of cytoskeleton and methodological aspects

“…However, development of DNA vaccines requires the design of plasmids allowing efficient expression of identified and well‐characterized epitopes of for instance viral glycoproteins with the potential to elicit a humoral and/or cellular immune response. The expression of gD‐1 is a candidate for an HSV‐1DNA‐vaccine (38, 39), because cell lines expressing abundant gD‐1 are resistant to HSV‐1 infection (107, 193). Contrary to gD‐1, plenty of gC‐1 is cytotoxic (264), which is why gC‐1 is probably ruled out in prophylaxis and therapy.…”

“…Their attraction is due to their abilities to remain latent in their host for life, to be reactivated, to cause a variety of infections, and there is still no final cure or effective vaccination available. Insights in the herpesvirus‐cell interactions are of general cell biological interest, especially to studies of DNA and RNA biogenesis (31) and intracellular transport (32), and of considerable significance in the efforts to generate antiviral (32–34) and anticancer (35–37) treatments, vaccines (38, 39), and gene therapy of, for instance, stroke, human immunodeficiency virus (HIV) infections, cancer and graft‐versus‐host diseases (40–43). The heavy reliance of viruses on the normal functions of the host cell and the latent stage make it difficult to prepare an effective vaccine or drug that interferes with the replication of the virus without simultaneously damaging the host cell.…”