MODIFIED HERPES SIMPLEX VIRUS AS AN SIV VACCINE VECTOR

改良单纯疱疹病毒作为 SIV 疫苗载体

• 批准号: 2555255
• 负责人: Ann B Hill
• 金额: $ 21.73万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-09-30 至 1999-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2555255
• 关键词: AIDS vaccines; Alphaherpesvirinae; Macaca mulatta; cytotoxic T lymphocyte; latent virus infection; polymerase chain reaction; simian AIDSs; simian immunodeficiency virus; spinal ganglion; tissue /cell culture; vaccinia virus; vector vaccine

DESCRIPTION (adapted from applicant's abstract): Infection with live attenuated simian immunodeficiency virus (SIV) can protect adult monkeys against a subsequent infection with virulent SIV. Both, the antibody and cytotoxic T lymphocyte (CTL) responses are probably necessary for protection, and to date all protective immunity has been associated with persistence of vaccine virus. Currently, a major goal of vaccine research is to understand the essential features of protective immunity engendered by live attenuated SIV and to safely recreate it in a clinically acceptable formulation. This proposal is for a preliminary investigation of a novel vaccine approach for persistent presentation of SIV antigen to CTL in vivo. An attenuated herpes simplex virus expressing SIV gag will be generated; the ability of this vector to induce a CTL response and to establish latent infection in rhesus monkeys will be established. HSV normally encodes a protein, ICP47, which blocks TAP, the transporter associated with antigen processing - and interferes with antigen presentation to CTL. SIV mac 251 gag coding sequences will be introduced into an HSV which has been engineered to lack ICP47; and a rescue virus then created which expresses functional ICP47. These two viruses will be used to immunize rhesus monkeys expressing the MHC class I alleles MamuA01, and the CTL responses to the immunodominant gag epitope pcll will be compared quantitatively and qualitatively with those induced by recombinant vaccinia virus expressing SIV gag. Immunized animals will be challenged intravenously with SIV mac251; and virus load assessed by virus isolation and branched DNA amplification of plasma viral RNA. Control challenge groups will include unimmunized animals and animals immunized with vaccinia and HSV vectors alone. At necropsy, the extent of virus latency in dorsal root ganglia established by HSV with and without functional ICP47 will be assessed.

描述（改编自申请人的摘要）：现场感染 衰减的邻苯二甲酸免疫缺陷病毒（SIV）可以保护成人猴子 反对随后感染有毒的SIV。 两者都是抗体和 细胞毒性T淋巴细胞（CTL）反应可能是必需的 保护，迄今为止，所有保护性免疫都与 疫苗病毒的持久性。 目前，疫苗研究的主要目标 是了解保护性免疫的基本特征 现场衰减SIV并在临床上可以接受的安全重新创建它 配方。 该建议是针对新型疫苗方法的初步研究 为了将SIV抗原持续向体内CTL呈现。 衰减 将产生表达SIV插科打g的单纯疱疹病毒；能力 该向量引起CTL反应并建立潜在感染 将建立恒河猴。 HSV通常编码蛋白质ICP47， 阻止TAP的转运蛋白与抗原加工相关联 - 和 干扰抗原呈递对CTL。 SIV Mac 251插科打码 序列将被引入已设计为缺乏的HSV ICP47;然后创建了一种表达功能性ICP47的救援病毒。 这两种病毒将用于免疫表达MHC的恒河猴 I级等位基因MAMUA01，以及CTL对免疫疾病的反应 表位PCLL将与这些pcll进行定量和定性比较 由表达SIV GAG的重组疫苗病毒诱导。 免疫动物 SIV MAC251将受到静脉内挑战；和病毒负荷评估 血浆病毒RNA的病毒分离和分支DNA扩增。 控制 挑战小组将包括未免疫的动物和接受免疫的动物 疫苗和HSV载体。 在尸检时，病毒潜伏期的程度 HSV建立有和没有功能的ICP47的背根神经节 将被评估。