Vaccine therapy for ocular herpes simplex virus (HSV) infection: periocular vaccination reduces spontaneous ocular HSV type 1 shedding in latently infected rabbits.
Periocular vaccination of rabbits with preexisting herpes simplex virus type 1 (HSV-1) latent infection with recombinant HSV-2 glycoproteins B and D (gB2 and gD2) plus adjuvant significantly reduced ocular viral shedding. Rabbits were infected in both eyes with HSV-1 strain McKrae. Following HSV-1 infection and the establishment of latency (28 days postinfection), rabbits were given a periocular subconjunctival vaccination three times at 3-week intervals. Beginning 3 weeks after the final vaccination, tear films were collected daily and cultured to detect the presence of HSV-1 and determine the spontaneous HSV-1 ocular shedding rates. Periocular vaccination increased the mean HSV-1 serum neutralizing antibody titer to fivefold above that seen in mock-vaccinated latently infected rabbits. gB enzyme-linked immunosorbent assay (ELISA) antibody titers were increased approximately 8-fold, and gD ELISA antibody titers were increased 60-fold. These increases were all statistically significant (P < 0.0001). In two independent experiments, vaccination reduced the spontaneous shedding rate by approximately 2.5-fold (P < 0.0004). In addition, the percentage of eyes that never shed virus during the 6 week postvaccination test period increased threefold (20% in controls versus 60% in vaccinated animals; P < 0.007). These results show that spontaneous ocular shedding of HSV-1 in latently infected rabbits can be significantly reduced by local periocular vaccination. This is the first report in any animal model of a successful therapeutic vaccine against recurrent HSV-1 ocular shedding. These results support the concept that development of a therapeutic vaccine for ocular HSV-1 recurrence in humans is possible.
Cedars-Sinai Medical Center, Los Angeles, California 90048.
A B
AB
Nesburn
R L
RL
Burke
H
H
Ghiasi
S
S
Slanina
S
S
Bahri
S L
SL
Wechsler
D000818:Animals; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D018259:Herpesvirus 1, Human / Q000254:growth & development / Q000502:physiology*; D018258:Herpesvirus 2, Human / Q000276:immunology; D016849:Keratitis, Herpetic / Q000276:immunology / Q000628:therapy*; D009500:Neutralization Tests; D011817:Rabbits; D014614:Vaccines, Synthetic / Q000627:therapeutic use; D014759:Viral Envelope Proteins / Q000276:immunology; D014765:Viral Vaccines / Q000627:therapeutic use*; D017735:Virus Latency; D017201:Virus Shedding
D014614:Vaccines, Synthetic; D014759:Viral Envelope Proteins; D014765:Viral Vaccines; C044525:glycoprotein B, herpes simplex virus type 2; C040570:glycoprotein D-herpes simplex virus type 2