HIV DOMAINS IMPORTANT FOR ANTIBODY NEUTRALIZATION

HIV 结构域对于抗体中和很重要

• 批准号: 3138970
• 负责人: DAVID D HO
• 金额: $ 20.2万
• 依托单位: CEDARS-SINAI MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-02-01 至 1991-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3138970
• 关键词: AIDS; affinity chromatography; antibody neutralization test; antigen antibody reaction; antiserum; antiviral agents; antiviral antibody; blocking antibody; enzyme linked immunosorbent assay; gel electrophoresis; genetic recombination; glycoproteins; human immunodeficiency virus 1; human tissue; immunofluorescence technique; immunoglobulin structure; immunological substance; laboratory mouse; laboratory rabbit; serology /serodiagnosis; synthetic peptide; tissue /cell culture; viral vaccines; virus antigen; virus envelope; virus morphology; virus protein

AIDS and HIV infection have reached epidemic proportions and a vaccine, as well as effective treatment, is urgently needed. Better understanding of HIV neutralizing antibodies is critical to the vaccine effort. Previous studies by several investigators, including the PI, have shown that HIV neutralizing antibodies (1) can be detected in serum of most infected individuals, (2) are primarily directed against envelope glycoproteins, gp 120 and gp 41, and (3) from human sera can neutralize diverse heterologous HIV isolates, although antibodies elicited in animals generally show type- specific neutralization. In addition, utilizing antisera raised against synthetic oligopeptides, the PI has identified four domains in gp d120 and gp 41 which are targets for neutralization. Furthermore, preliminary findings suggest that there may be envelope domains which can elicit antibodies capable of either enhancing HIV infection in vitro or blocking the action of neutralizing antibodies. The proposed investigations will employ two major approaches to define the domains important in HIV neutralization. The first will utilize recombinant and synthetic peptides to isolate specific immunoglobulin fractions from human neutralizing sera by affinity chromatography. The second will involve immunization of laboratory animals with recombinant and synthetic peptides to raise specific antisera. In a neutralization assay, the activity of these mono-specific human and animal antibody preparations to neutralize HIV will be determined using multiple diverse isolates. Subsequently, studies will be initiated to explore the mechanism of action of neutralizing antibodies. In addition, the non- neutralizing antibodies will be examined for possible enhancement of HIV infection and for blocking effect on neutralizing antibodies. The results of these studies may form the basis for the rational design of a vaccine for AIDS.

艾滋病和艾滋病毒感染已达到流行比例，并且 迫切需要疫苗以及有效的治疗。 更好地了解中和抗体对 疫苗的工作。 包括PI在内的几位研究人员的先前研究 表明可以在 大多数感染者的血清（2）主要是指向的 反对信封糖蛋白，GP 120和GP 41，以及（3） 人血清可以中和多种异源HIV分离株， 尽管动物引起的抗体通常显示出类型 - 特定中和。 另外，利用抗血清升高 反对合成寡肽，PI鉴定了四个域 在GP D120和GP 41中，这是中和的靶标。 此外，初步发现表明 可以引起能够任何一种的抗体的信封域 在体外增强HIV感染或阻止 中和抗体。 拟议的调查将采用两种主要方法 定义在HIV中和重要的领域。 第一个意愿 利用重组和合成肽隔离特异性 来自人类中和血清的免疫球蛋白部分由 亲和色谱。 第二个将涉及免疫 具有重组和合成肽的实验动物 提出特定的抗血清。 在中和测定中， 这些单一特异性的人和动物抗体制剂 中和艾滋病毒将使用多种不同的分离株确定。 随后，将开始研究以探索机制 中和抗体的作用。 另外，非 将检查中和抗体以进行可能增强 HIV感染和中和的阻塞效应 抗体。 这些研究的结果可能是 艾滋病疫苗的合理设计。