VACCINE ADJUVANT FOR AIDS

该建议将集中在大分子组装方法， 设计和测试艾滋病毒疫苗佐剂配方， 系统的，化学上明确的方式。 大分子 我们实验室最近开发的组装方法是一个系统， 重组各种细胞成分以模拟整个生物体 允许评估其对豁免的贡献，包括 寡聚肽抗原的支架称为多重 抗原肽系统（MAPS），脂质膜锚定部分，脂质 基质和脂溶性佐剂。 它还允许灵活性， 呈递肽和蛋白质抗原的混合物，包括 重组gp 120，在脂质体或脂质基质中。 带有内置 脂质膜锚（LipoMAPS）已被证明是B细胞促分裂原， 细胞因子诱导剂和有效的抗原特异性佐剂。 立即 该项目的目标是开发具有gp 120的lipoMAPS， 脂质体作为新的抗原特异性佐剂制剂 HIV- 1的疫苗，长期目标是开发一种 有效且临床上可接受佐剂制剂和疫苗 对抗HIV-1。 具体目标是： 1.在脂质体中开发稳定有效的分子组装体， 脂质基质，并在小动物中测试它们的诱导功效 体液和细胞介导的免疫，包括刺激 细胞因子和CTL。 2.研究脂质锚定物的佐剂作用和脂质锚定物的协同作用。 大分子组合物中的外来亲脂性佐剂 approach. 3.用包埋的重组gp 120测试LipoMAPS， 大分子组合物作为一种新的抗原特异性佐剂， 诱导类型和组特异性体液应答，以及 细胞免疫 4.在小动物中测试LipoMAPS刺激粘膜的功效 免疫力 5.发展了呈现B- 和T细胞表位来克服不同HIV-1的抗原多样性 分离株

This proposal will focus on the macromolecular assemblage approach to design and test HIV vaccine adjuvant formulations in a rational systematic, and chemically unambiguous manner. The macromolecular assemblage approach recently developed in our laboratory is a system of reconstituting various cellular components to mimic the whole organism that allows evaluation of their contribution to immunity and includes oligomeric peptide antigens on a scaffolding known as the multiple antigen peptide system (MAPS), lipid membrane-anchoring moieties, lipid matrices and lipid soluble adjuvants. It also allows the flexibility in presenting mixtures of peptide and protein antigens, including recombinant gpl2O, in liposomes or lipid matrices. MAPS with a built-in lipid membrane anchor (LipoMAPS) have been shown to be a B-cell mitogen, a cytokine inducer and a potent antigen-specific adjuvant. The immediate goal of this project is the development of lipoMAPS with gp 120 in liposomes as a novel and antigen-specific adjuvant formulation for vaccines against HIV- 1 and the long term goal is the development of an effective and clinically acceptable adjuvant formulation and vaccine against HIV-1. The specific aims are: 1. Develop stable and effective molecular assemblage in liposomes and lipid matrices and test their efficacy in small animals for elicitation of humoral and cell-mediated immunities, including the stimulation of cytokines and CTLs. 2. Study the adjuvant effects of lipid anchors and synergism of extraneous lipophilic adjuvants in the macromolecular assemblage approach. 3. Test LipoMAPS with the entrapped recombinant gpl2O in the macromolecular assemblage as a novel and antigen-specific adjuvant in inducing type- and group-specific humoral responses as well as cell-mediated immunities. 4. Test efficacy of LipoMAPS in small animals to stimulate mucosal immunity. 5. Develop the molecular assemblage approach of presenting mixtures of B- and T-cell epitopes to overcome the antigen diversity of different HIV-1 isolates.