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.
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.
Frye
T D
TD
Department of Anatomy, Wright State University, Dayton, Ohio 45435, USA.
Chiou
H C
HC
Hull
B E
BE
Bigley
N J
NJ
D000818:Animals; D001212:Asialoglycoproteins / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D005260:Female; D022301:Herpes Simplex Virus Vaccines / Q000276:immunology*; D018259:Herpesvirus 1, Human / Q000276:immunology*; D007114:Immunization; D016849:Keratitis, Herpetic / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D009961:Orosomucoid / Q000031:analogs & derivatives* / Q000276:immunology; D012668:Trigeminal Ganglion / Q000821:virology; D019444:Vaccines, DNA / Q000276:immunology*; D014759:Viral Envelope Proteins / Q000276:immunology*; D019562:Viral Load
D001212:Asialoglycoproteins; D022301:Herpes Simplex Virus Vaccines; D009961:Orosomucoid; D019444:Vaccines, DNA; D014759:Viral Envelope Proteins; C017030:asialoorosomucoid; C039447:glycoprotein D, Human herpesvirus 1