AUGMENTING IMMUNE RESPONSES TO WEAK IMMUNOGENS

增强对弱免疫原的免疫反应

• 批准号: 3546825
• 负责人: George K Lewis
• 金额: $ 11.01万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 1987
• 资助国家: 美国
• 起止时间: 1987-09-30 至 1991-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3546825
• 关键词: AIDS; Freund's adjuvant; antibody neutralization test; antiviral antibody; arsenic; azobenzene; enzyme linked immunosorbent assay; helper T lymphocyte; high performance liquid chromatography; human immunodeficiency virus 1; immunization; immunoconjugates; immunological substance; immunomodulators; laboratory mouse; peptide chemical synthesis; peptide structure; poliovirus; protein engineering; synthetic antigens; synthetic peptide; synthetic vaccines; tyrosine; vaccinia virus; viral vaccines; virus antigen; virus envelope; virus protein

The recent revolution in vaccine development has renewed the need for simple and general methods to increase antibody responses to weak immunogens. Accordingly, the present research is aimed at development of such a method to optimize antibody responses to antigenic peptides. The long term goal of the proposed research is to achieve a completely synthetic immunogen comprised of an adjuvant moiety, a carrier determinant that only stimulates T cells, and an antigenic peptide against which antibody will be made. Development of this system will circumvent several of the problems inherent in the traditional peptide-vaccine method where the antigenic peptide is conjugated to a protein carrier. The research will proceed in two stages. The first stage will focus on the antigenic peptide-carrier conjugate. A small (m.w. = 409) synthetic carrier determinant, L- Tyrosine-P-azobenzenearsonate (ABA-Try) will be evaluated in three anti-peptide response system (one poliovirus VPI peptide, and two HIV env peptides). Special emphasis will be placed on elucidation of antigen-structural variables as they affect immunogenicity. In particular the spacing and orientation of the antigentic peptide relative to the carrier determinant ABA-Tyr will be investigated. The second stage will build upon the first by investigating the attachment of a synthetic adjuvant moiety to each of the optimal conjugates. Emphasis in this stage will be placed on the nature of the moiety and its spacing and orientation relative to the antigenic peptide and carrier determinant. Because the second phase is entirely dependent upon success in the first phase, funding is initially requested only for the first phase which can be completed in 3 years.

最近的疫苗开发革命更新了 需要简单和通用的方法来增加抗体 对弱免疫原的反应。 因此，本 研究的目的是开发这样一种方法来优化 抗体对抗原肽的反应。 的长期目标 这项研究旨在实现一种完全合成的 包含佐剂部分、载体 仅刺激T细胞的决定簇，和抗原肽 将针对其制备抗体。 本系统开发 将规避传统方法固有的几个问题 抗原肽结合的肽疫苗法 到蛋白质载体。 研究将分两个阶段进行。 第一阶段将集中在抗原肽载体 共轭 一个小的（M. W.）= 409）合成载体决定簇，L- 酪氨酸-对-偶氮苯胂酸盐（ABA-Try）将在 三种抗肽应答系统（一种脊髓灰质炎病毒VPI肽， 和两种HIV env肽）。 将特别强调 阐明抗原结构变量，因为它们影响 免疫原性 特别是， 相对于载体决定簇ABA-Tyr的抗原肽 将进行调查。 第二阶段将以第一阶段为基础， 研究合成佐剂部分与 每一个最佳共轭物。 本阶段的重点将是 取决于该部分的性质及其间距和取向 相对于抗原肽和载体决定簇。 因为第二阶段完全取决于 在第一阶段，最初只为第一阶段申请资金， 这一阶段可以在三年内完成。