SYNCYTIUM INHIBITION ANTIBODIES AND MATERNAL-INFANT AIDS

合胞体抑制抗体与母婴艾滋病

• 批准号: 3147445
• 负责人: WARREN A ANDIMAN
• 金额: $ 31.69万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-09-30 至 1995-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3147445
• 关键词: AIDS; AIDS /HIV diagnosis; HIV infections; communicable disease transmission; congenital infection; female; gene expression; genetic strain; human immunodeficiency virus 1; human subject; infant human (0-1 year); neutralizing antibody; pediatric AIDS; placental transfer; polymerase chain reaction; serology /serodiagnosis; tissue /cell culture; virus antigen; virus cytopathogenic effect; virus envelope

HIV-1 is transmitted from infected mothers to their infants at a rate of less than 30 percent. The rate of transmission and the expression of disease in the offspring are probably modulated by both humoral and cell-mediated responses in mother and child and by the biologic characteristics of the infecting strain of HIV-1. Previous studies in this laboratory have resulted in the development of an HIV-1 syncytium-inhibition assay which makes use of several unique cell lines. Preliminary work point to a marked difference in the prevalence and titer of syncytium inhibition (SI) antibodies in children who survive longer compared to those who succumb to opportunistic infections in the first 1-2 years of life. It is likely that these SI antibodies exert a protective effect in children and may modulate the rate of vertical transmission. Hence, studies are planned to examine further the relationship between the prevalence and titer of SI antibodies and clinical expression of HIV-1 disease in children. Studies will be expanded to include analysis of maternal sera in order to learn whether SI antibody also affects clinical expression of disease in the mother or alters the rate of vertical transmission. Experiments will also be undertaken to learn whether the titer of SI antibody is affected by the HIV-1 strain used in the target cell system or by the cell type in which the virus resides. Genetic expression systems and both monoclonal and polyclonal antibodies will be used in order to identify the epitopes responsible for eliciting SI antibodies. In order to study the virologic correlates of SI antibody production in women and children, the association between SI antibody titer, plasma and cell-associated viremia and p24 antigen production will be determined. In the process, a variety of HIV-1 strains will be isolated, cultivated, and characterized biologically. These studies have implications for both vaccine development and passive immunotherapy.

HIV-1从受感染的母亲传染给婴儿的速度为 低于30%。 传播率和表达 后代中的疾病可能受到体液和 母亲和孩子的细胞介导的反应，以及生物 HIV-1感染株的特征。 以前的研究在此 实验室已经开发出一种HIV-1 合胞体抑制测定，其利用几种独特的细胞系。 初步工作指出，在患病率和滴度上有显著差异， 合胞体抑制（SI）抗体在儿童谁生存时间较长 与那些死于前1-2年机会性感染的人相比， 多年的生活。 很可能这些SI抗体发挥保护作用， 影响儿童，并可能调节垂直传播率。 因此，计划进行研究，以进一步探讨 SI抗体的流行率和滴度以及HIV-1的临床表达 儿童疾病。 研究将扩大到包括分析 母亲血清，以了解SI抗体是否也影响临床 疾病在母亲中的表达或改变垂直 传输 还将进行实验，以了解 SI抗体的滴度受目标中使用的HIV-1毒株的影响 细胞系统或病毒所在的细胞类型。 遗传 表达系统以及单克隆和多克隆抗体将被 用于鉴定引起SI的表位 抗体的 为了研究SI抗体的病毒学相关性， 在妇女和儿童的生产，SI抗体之间的关联 滴度、血浆和细胞相关的病毒血症和p24抗原产生将 被确定。 在这个过程中，各种HIV-1菌株将被 分离、培养和生物学特性鉴定。 这些研究 对疫苗开发和被动免疫治疗的影响。