Department of Molecular Microbiology and Immunology, Saint Louis University School of Medicine, St. Louis, Missouri, United States of America.
PLoS One. 2011;6(8):e22772. doi: 10.1371/journal.pone.0022772. Epub 2011 Aug 3.
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.
单纯疱疹病毒 1 型（HSV-1）可引起疱疹性基质角膜炎（HSK），这是一种威胁视力的角膜疾病，目前尚无疫苗。一种复制缺陷型、缺失 ICP8 和病毒宿主关闭（vhs）蛋白编码基因的 HSV-1 原型疫苗可降低 HSK 小鼠模型中的 HSV-1 复制和疾病。在这里，我们证明了与 ICP8-vhs-亲本株相比，缺失 ICP8 和 vhs 与基于病毒的 B7 共刺激分子表达的组合产生了一种疫苗株，增强了对 HSV-1 的 T 细胞反应，并降低了角膜挑战后角膜炎和中枢神经系统急性感染的发生率。挑战后的三叉神经节 T 细胞浸润和局部淋巴结中的抗原特异性回忆反应与保护相关。因此，从复制缺陷型、ICP8-vhs-病毒基因组中表达的 B7 共刺激分子通过进一步降低 HSK 来增强疫苗效力。
