title: B7 costimulation molecules encoded by replication-defective, vhs-deficient HSV-1 improve vaccine-induced protection against corneal disease.
abstract: Herpes simplex virus 1 (HSV-1) causes herpes stromal keratitis (HSK), a sight-threatening disease of the cornea for which no vaccine exists. A replication-defective, HSV-1 prototype vaccine bearing deletions in the genes encoding ICP8 and the virion host shutoff (vhs) protein reduces HSV-1 replication and disease in a mouse model of HSK. Here we demonstrate that combining deletion of ICP8 and vhs with virus-based expression of B7 costimulation molecules created a vaccine strain that enhanced T cell responses to HSV-1 compared with the ICP8⁻vhs⁻ parental strain, and reduced the incidence of keratitis and acute infection of the nervous system after corneal challenge. Post-challenge T cell infiltration of the trigeminal ganglia and antigen-specific recall responses in local lymph nodes correlated with protection. Thus, B7 costimulation molecules expressed from the genome of a replication-defective, ICP8⁻vhs⁻ virus enhance vaccine efficacy by further reducing HSK.
authors.affiliation: Department of Molecular Microbiology and Immunology, Saint Louis University School of Medicine, St. Louis, Missouri, United States of America.
authors.forename: Jane E
authors.initials: JE
authors.lastname: Schrimpf
authors.forename: Eleain M
authors.initials: EM
authors.lastname: Tu
authors.forename: Hong
authors.initials: H
authors.lastname: Wang
authors.forename: Yee M
authors.initials: YM
authors.lastname: Wong
authors.forename: Lynda A
authors.initials: LA
authors.lastname: Morrison
mesh_terms: D000818:Animals; D060887:B7 Antigens / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D018122:B7-1 Antigen / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D051940:B7-2 Antigen / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D015139:Blotting, Southern; D002460:Cell Line; D002522:Chlorocebus aethiops; D003316:Corneal Diseases / Q000276:immunology* / Q000821:virology*; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D018259:Herpesvirus 1, Human / Q000235:genetics / Q000276:immunology*; D007376:Interleukin-2; D016849:Keratitis, Herpetic / Q000276:immunology* / Q000821:virology*; D051379:Mice; D060888:Real-Time Polymerase Chain Reaction; D014764:Viral Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D014779:Virus Replication / Q000235:genetics / Q000276:immunology
chemical_list: D060887:B7 Antigens; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D007376:Interleukin-2; D014764:Viral Proteins