EPITOPE DISCOVERY--A NEW ROUTE TO VACCINES

表位的发现——疫苗的新途径

• 批准号: 2734619
• 负责人: GEORGE PEARSON SMITH
• 金额: $ 16.42万
• 依托单位: UNIVERSITY OF MISSOURI-COLUMBIA
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-07-01 至 2000-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2734619
• 关键词: B lymphocyte; T lymphocyte; active immunization; antibody formation; antigen antibody reaction; antigens; bacteriophage T4; enzyme linked immunosorbent assay; immunoglobulin G; laboratory mouse; leukocyte activation /transformation; tissue /cell culture; vaccine development

Bacteriophage T4 serves as a model ~pathogen~ for evaluation a new vaccine development strategy called epitope discovery. The goal is to find artificial mimics of authentic pathogen B-epitopes that can serve as components of an effective vaccine. The source of mimics are large libraries of random peptides genetically fused to the surface of filamentous phage-display vectors. Mouse anti-pathogen antibodies--we call them direct antibodies because they are elicted directly by the pathogen--have been used to affinity select clones out of the phage libraries whose displayed peptides bind them strongly. These peptides are antigenic mimics of the corresponding authentic pathogen epitopes. Are they also immunogenic mimics, in the sense that they elicit an antibody response that cross-reacts with the pathogen itself? That is a vital question in evaluating the promise of epitope discovery for vaccine development, since only immunogenic mimics can have disease-protective value. Accordingly, a panel of antigenic mimics will be assessed for two key components of immunogenic mimicry. First, mice will be hypperimmunized with each of the antigenic mimics and the resulting indirect antibodies titered against both the antigenic mimic and the authentic pathogen epitope. Comparable titers would indicate that the former is a good immunogenic mimic of the latter. Second, mice will be primed with antigenic mimics (long with appropriate T epitopes) to determine if the resulting memory B cells can be mobilized by a challenge with the pathogen itself.

噬菌体T4作为模型病原体评价一种新的 疫苗开发战略称为表位发现。我们的目标是 寻找人工模拟真实病原体B表位的方法 作为有效疫苗的组成部分。模仿的源泉 是随机多肽的大型文库在基因上与 丝状噬菌体展示载体的表面。小鼠抗病原 抗体--我们称它们为直接抗体，因为它们是由 直接由病原体--已被用来亲和选择克隆 从展示了结合它们的多肽的噬菌体文库中 非常强烈。这些多肽是相应的 真正的病原体表位。它们是不是也是免疫原性模拟物， 从某种意义上说，它们会引起抗体反应，从而产生交叉反应 与病原体本身有关吗？这是评估 为疫苗开发发现表位的承诺，因为只有 免疫原性模拟物可以具有预防疾病的价值。 因此，一组抗原性模拟物将被评估为两个 免疫原性拟态的关键成分。首先，老鼠将成为 用每一种抗原模拟物和 产生的间接抗体对这两种抗原模拟物进行滴定 和真正的病原体表位。类似的效价将 提示前者是后者的良好免疫原性模拟物。 其次，小鼠将被注射抗原性模拟物(长时间 适当的T表位)，以确定所产生的记忆B细胞 可以通过对病原体本身的挑战来动员。