title: Protection against recurrent ocular herpes simplex virus type 1 disease after therapeutic vaccination of latently infected mice.
abstract: The potential of therapeutic vaccination of animals latently infected with herpes simplex virus type 1 (HSV-1) to enhance protective immunity to the virus and thereby reduce the incidence and severity of recurrent ocular disease was assessed in a mouse model. Mice latently infected with HSV-1 were vaccinated intranasally with a mixture of HSV-1 glycoproteins and recombinant Escherichia coli heat-labile enterotoxin B subunit (rEtxB) as an adjuvant. The systemic immune response induced was characterized by high levels of virus-specific immunoglobulin G1 (IgG1) in serum and very low levels of IgG2a. Mucosal immunity was demonstrated by high levels of IgA in eye and vaginal secretions. Proliferating T cells from lymph nodes of vaccinated animals produced higher levels of interleukin-10 (IL-10) than were produced by such cells from mock-vaccinated animals. This profile suggests that vaccination of latently infected mice modulates the Th1-dominated proinflammatory response usually induced upon infection. After reactivation of latent virus by UV irradiation, vaccinated mice showed reduced viral shedding in tears as well as a reduction in the incidence of recurrent herpetic corneal epithelial disease and stromal disease compared with mock-vaccinated mice. Moreover, vaccinated mice developing recurrent ocular disease showed less severe signs and a quicker recovery rate. Spread of virus to other areas close to the eye, such as the eyelid, was also significantly reduced. Encephalitis occurred in a small percentage (11%) of mock-vaccinated mice, but vaccinated animals were completely protected from such disease. The possible immune mechanisms involved in protection against recurrent ocular herpetic disease in therapeutically vaccinated animals are discussed.
authors.affiliation: Department of Pathology and Microbiology, School of Medical Sciences, University of Bristol, Bristol BS8 1TD, United Kingdom. Claire.M.Richards@bristol.ac.uk
authors.forename: C M
authors.initials: CM
authors.lastname: Richards
authors.forename: R
authors.initials: R
authors.lastname: Case
authors.forename: T R
authors.initials: TR
authors.lastname: Hirst
authors.forename: T J
authors.initials: TJ
authors.lastname: Hill
authors.forename: N A
authors.initials: NA
authors.lastname: Williams
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D005260:Female; D018259:Herpesvirus 1, Human / Q000276:immunology* / Q000502:physiology*; D022283:Herpesvirus Vaccines / Q000008:administration & dosage / Q000627:therapeutic use*; D007114:Immunization; D016849:Keratitis, Herpetic / Q000188:drug therapy / Q000517:prevention & control*; D051379:Mice; D012008:Recurrence; D013601:T-Lymphocytes / Q000276:immunology; D014611:Vaccination; D014775:Virus Activation; D017735:Virus Latency; D017201:Virus Shedding
chemical_list: D000914:Antibodies, Viral; D022283:Herpesvirus Vaccines