title: Local periocular vaccination protects against eye disease more effectively than systemic vaccination following primary ocular herpes simplex virus infection in rabbits.
abstract: Vaccination of experimental animals can provide efficient protection against ocular herpes simplex virus type 1 (HSV-1) challenge. Although it is suspected that local immune responses are important in protection against ocular HSV-1 infection, no definitive studies have been done to determine if local ocular vaccination would produce more efficacious protection against HSV-1 ocular challenge than systemic vaccination. To address this question, we vaccinated groups of rabbits either systemically or periocularly with recombinant HSV-2 glycoproteins B (gB2) and D (gD2) in MF59 emulsion or with live KOS (a nonneurovirulent strain of HSV-1). Three weeks after the final vaccination, all eyes were challenged with McKrae (a virulent, eye disease-producing strain of HSV-1). Systemic vaccination with either HSV-1 KOS or gB2/gD2 in MF59 did not provide significant protection against any of the four eye disease parameters measured (conjunctivitis, iritis, epithelial keratitis, and corneal clouding). In contrast, periocular vaccination with gB2/gD2 in MF59 provided significant protection against conjunctivitis and iritis, while ocular vaccination with live HSV-1 KOS provided significant protection against all four parameters. Thus, local ocular vaccination provided better protection than systemic vaccination against eye disease following ocular HSV-1 infection. Since local vaccination should produce a stronger local immune response than systemic vaccination, these results suggest that the local ocular immune response is very important in protecting against eye disease due to primary HSV-1 infection. Thus, for clinical protection against primary HSV-1-induced corneal disease, a local ocular vaccine may prove more effective than systemic vaccination.
authors.affiliation: Ophthalmology Research Laboratories, Cedars-Sinai Medical Center, Los Angeles, California, USA.
authors.forename: A B
authors.initials: AB
authors.lastname: Nesburn
authors.forename: S
authors.initials: S
authors.lastname: Slanina
authors.forename: R L
authors.initials: RL
authors.lastname: Burke
authors.forename: H
authors.initials: H
authors.lastname: Ghiasi
authors.forename: S
authors.initials: S
authors.lastname: Bahri
authors.forename: S L
authors.initials: SL
authors.lastname: Wechsler
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000818:Animals; D005123:Eye; D016849:Keratitis, Herpetic / Q000276:immunology / Q000517:prevention & control*; D011136:Polysorbates / Q000008:administration & dosage; D011817:Rabbits; D018139:Simplexvirus / Q000276:immunology; D013185:Squalene / Q000008:administration & dosage; D014614:Vaccines, Synthetic / Q000008:administration & dosage; D014765:Viral Vaccines / Q000008:administration & dosage*
chemical_list: D000276:Adjuvants, Immunologic; C089950:MF59 oil emulsion; D011136:Polysorbates; D014614:Vaccines, Synthetic; D014765:Viral Vaccines; D013185:Squalene