AUGMENTING IMMUNE RESPONSES TO WEAK IMMUNOGENETICS

最近疫苗开发的革命更新了 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，现在 研究的目的是开发这样一种优化方法 对抗原肽的抗体反应。的长期目标是 提出的研究是为了实现完全综合的 免疫基因由佐剂部分、载体 只刺激T细胞的决定簇，以及抗原肽 其中的抗体将被制成。本系统的开发 将绕过传统的 抗原肽偶联的多肽疫苗方法 一种蛋白质载体。研究将分两个阶段进行。 第一阶段将集中在抗原肽载体上 共轭。小型(M.W.=409)合成载体决定簇，L- 酪氨酸-对偶氮苯亚胺(ABA-Try)将在#年进行评估 三个抗肽反应系统(一个脊髓灰质炎病毒VPI肽， 和两个HIV包膜多肽)。我们将特别强调 阐明影响抗原结构变量的因素 免疫原性。的间距和方向 与载体决定簇ABA-Tyr相关的抗原肽 将会被调查。第二阶段将在第一阶段的基础上进行 研究合成佐剂部分与 每一种最佳的共轭。此阶段的重点将是 放在部分的性质及其间隔和方向上 相对于抗原肽和载体决定簇。 因为第二阶段完全依赖于 第一阶段，最初只为第一阶段申请资金 这一阶段可以在3年内完成。

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.