EPITOPE DISCOVERY--A NEW ROUTE TO VACCINES

表位的发现——疫苗的新途径

• 批准号: 2397620
• 负责人: GEORGE PEARSON SMITH
• 金额: $ 15.94万
• 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 1999-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2397620
• 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作为一种模式病原体用于评估一种新的 疫苗开发策略称为表位发现。 目标是 寻找真实病原体B表位的人工模拟物， 作为有效疫苗的组成部分。 模仿的来源 是随机肽的大型文库， 丝状噬菌体展示载体的表面。 小鼠抗病原体 抗体，我们称之为直接抗体，因为 直接通过病原体--已经被用于亲和选择克隆 从噬菌体文库中分离出来， 强烈地。 这些肽是相应的多肽的抗原模拟物。 真正的病原体表位。 它们是否也是免疫原性模仿物， 在某种意义上，它们引发了抗体反应， 与病原体本身的关系 这是评估 表位发现的疫苗开发的承诺，因为只有 免疫原性模拟物可具有疾病保护价值。 因此，将评估一组抗原模拟物的两个方面， 免疫原性拟态的关键成分 首先，老鼠将 用每种抗原模拟物超免疫， 产生的间接抗体针对抗原模拟物 和真正的病原体表位 可比滴度将 表明前者是后者的良好免疫原性模拟物。 第二，小鼠将用抗原模拟物（长时间用抗原模拟物）致敏。 合适的T表位）以确定所得到的记忆B细胞 可以被病原体本身的挑战所调动。