PROTECTIVE MECHANISM OF HERPES SIMPLEX VIRUS ANTIBODY

单纯疱疹病毒抗体的保护机制

• 批准号: 3264566
• 负责人: ROBERT N LAUSCH
• 金额: $ 15.03万
• 依托单位: UNIVERSITY OF SOUTH ALABAMA
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-04-01 至 1993-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3264566
• 关键词: Alphaherpesvirinae; T lymphocyte; antiantibody; antiviral antibody; cellular immunity; cornea disorder; cytotoxicity; disease /disorder model; enzyme linked immunosorbent assay; eye infections; fluorescence; glycoproteins; humoral immunity; immunization; immunoglobulins; laboratory mouse; monoclonal antibody; ocular herpes; passive transport; radioassay; tissue /cell culture; virus replication

Herpes simplex virus (HSV) is an important ocular pathogen in man. Following infection both cellular and humoral immune responses are elicited. However, the relative contribution that each makes toward limiting or exacerbating virus infection is poorly understood. We and other investigators have shown that passive transfer of HSV-specific monoclonal antibody (mcAb) will enable the host to resist a lethal challenge dose of virus. More recently, it has been found that mcAbs specific for HSV glycoproteins given 24 hours after corneal infection are able to prevent or ameloriate development of stromal disease and promote resolution of HSV eye infection. Using a murine ocular infection model, we propose to investigate basic aspects of how antibody can control HSV replication. McAbs specific for HSV glycoproteins, gD, and selected other glycoproteins, will be purified, characterized, and tested for their capacity to inhibit HSV replication and promote virus clearance from corneal tissue of the BALB/c mouse. In conducting this work, special emphasis will be placed on evaluating the importance of immunoglobulin isotype and epitope specificity. A primary goal is to investigate the mechanism(s) by which antibody can exert its protective effect. The hypothesis to be tested is that antibody-dependent cellular cytotoxicity is an important defense mechanism in vivo. The information gained from these studies will identify properties anti-HSV antibodies must have in order to protect optimally in vivo, and provide new insights into the role the humoral immune response plays in containing virus infection.

单纯疱疹病毒（HSV）是一种重要的眼部病原体， 伙计 感染后，细胞和体液免疫 反应被引出。 然而，相对贡献， 每种方法都有助于限制或加剧病毒感染， 不太了解。 我们和其他调查人员已经证明， HSV特异性单克隆抗体（McAb）的被动转移将 使宿主能够抵抗致命剂量的病毒攻击。 更 最近发现，HSV特异性McAb 角膜感染后24小时给予糖蛋白能够 预防或减轻间质疾病的发展， 促进HSV眼部感染的消退。 我们建议使用小鼠眼部感染模型进行研究 抗体如何控制HSV复制的基本方面。 对HSV糖蛋白、gD和选定的其他蛋白具有特异性的单克隆抗体 糖蛋白，将被纯化，表征，并测试其 抑制HSV复制和促进病毒清除的能力 从BALB/c小鼠的角膜组织。 进行这项 工作，将特别强调评估 免疫球蛋白同种型和表位特异性的重要性。 一 主要目的是研究抗体 可以发挥其保护作用。 待检验的假设是 抗体依赖性细胞毒性是 体内防御机制。 从这些研究中获得的信息将确定属性 抗HSV抗体必须具有，以便最佳地保护 体内，并提供新的见解的作用，体液免疫 反应在遏制病毒感染中发挥作用。