A therapeutic vaccine that reduces recurrent herpes simplex virus type 1 corneal disease.
OBJECTIVE
To investigate the therapeutic efficacy of periocular vaccination with herpes simplex virus (HSV) recombinant glycoprotein D from HSV-1 (gD1) or HSV-2 (gD2) in decreasing HSV-induced recurrent dendritic keratitis and HSV-induced recurrent ocular shedding in rabbits latently infected with HSV-1.


METHODS
Rabbits latently infected with HSV-1 were vaccinated periocularly (by subconjunctival injection) with gD1 and adjuvant, gD2 and adjuvant, or adjuvant alone. Eyes were examined daily for 49 days for recurrent herpetic keratitis and for recurrent infectious HSV-1 shedding.


RESULTS
In both vaccinated groups, a significantly decreased number of eyes exhibited recurrences of herpetic keratitis compared with recurrences in adjuvant-treated control eyes (gD1 group, 27/1372, [2%]; gD2 group, 24/1274, [2%]; and control, 54/1274 [4%]; P < 0.005). Eyes in the gD1-vaccinated group (44/1308 [3.4%]; P = 0.01), but not those in the gD2-vaccinated group (71/1274 [5.6%]; P = 0.93), had significantly decreased viral shedding (positive cultures compared with total cultures) compared with eyes in the adjuvant-treated control group (69 of 1275 [5.4%]).


CONCLUSIONS
Recurrent HSV-1 corneal disease was significantly reduced by therapeutic local periocular vaccination. The vaccine may be more efficacious against HSV-1-induced recurrent corneal disease than against recurrent HSV-1 ocular shedding. Its efficacy against corneal disease appeared to be longer lasting than its efficacy against recurrent spontaneous shedding. The heterotypic gD2 vaccine was as efficacious as the homotypic gD1 vaccine against recurrent corneal disease, whereas the homotypic vaccine was much more efficacious than the heterotypic vaccine against recurrent HSV-1 shedding. This is the first report in any animal model of a successful therapeutic vaccine against recurrent HSV-1-induced corneal disease. These results support the concept that development of a therapeutic vaccine for ocular HSV-1 recurrence in humans may be possible.
Nesburn
A B
AB
Ophthalmology Research, Cedars-Sinai Medical Center Burns and Allen Research Institute, Los Angeles, California 90048, USA.
Burke
R L
RL
Ghiasi
H
H
Slanina
S M
SM
Wechsler
S L
SL
D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000031:analogs & derivatives / Q000276:immunology; D000276:Adjuvants, Immunologic; D000818:Animals; D003315:Cornea / Q000821:virology*; D003588:Cytopathogenic Effect, Viral; D005260:Female; D018259:Herpesvirus 1, Human / Q000276:immunology* / Q000302:isolation & purification; D018258:Herpesvirus 2, Human / Q000276:immunology / Q000302:isolation & purification; D007635:Keratitis, Dendritic / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D010714:Phosphatidylethanolamines / Q000276:immunology; D011817:Rabbits; D012008:Recurrence; D012867:Skin / Q000821:virology; D013666:Tears / Q000821:virology; D014611:Vaccination; D019444:Vaccines, DNA / Q000008:administration & dosage; D014759:Viral Envelope Proteins / Q000276:immunology; D014765:Viral Vaccines / Q000008:administration & dosage*; D017201:Virus Shedding
D000276:Adjuvants, Immunologic; D010714:Phosphatidylethanolamines; D019444:Vaccines, DNA; D014759:Viral Envelope Proteins; D014765:Viral Vaccines; C039447:glycoprotein D, Human herpesvirus 1; C040570:glycoprotein D-herpes simplex virus type 2; C037144:mifamurtide; D000119:Acetylmuramyl-Alanyl-Isoglutamine