VACCINE ADJUVANTS FOR AIDS

该项目的总体目标是设计和开发一种 新型人类免疫缺陷病毒(HIV)疫苗 合成的，基于多肽的，含有多种抗原，无载体， 带有内置佐剂。这种新型合成疫苗的目标是 中发现的连接、载体和佐剂问题的改进 合成疫苗。建议的设计将包含多种多肽 与HIV相关的抗原，如T辅助诱导决定簇和B细胞 决定因素和佐剂，都附着在一个小的树突上 分支赖氨酰核心，称为多抗原肽(MAP)系统 是我们实验室最近开发出来的。此外，这些多肽抗原 而赖氨酸芯将被精确地布置为单个单元，并且 以化学上明确的方式合成的。此外，地图 系统外表面含有高密度的多肽抗原 (总分子量的90%)和只有一小部分支架赖氨酸 核(分子量的10%)。这些不同的特征也适用于 为了克服载波问题在设计中的障碍 基于多肽的疫苗。此外，设计的简单性也 提供修改和开发以增强 人类疫苗的免疫原性和长期稳定性。最后， 脂肪酸，脂质体形成或膜锚定部分偶联到 这些地图被提出为适当的模型，以减轻对 佐剂。因此，这个项目的长期目标是设计和 开发一种化学定义的，自给自足的，多种抗原， 无载体，以多肽为基础的疫苗，适合人类和保护性 对抗人类免疫缺陷病毒。 尽管我们已经证明了地图系统提供了一个极好的 在动物中引发免疫反应的原型模型，许多 地图系统的潜力尚未确定。我们的直接客户 目标是(1)优化地图模型的设计，即：大小， 外源多肽抗原的排列、化学计量关系和 小分支赖氨酰核心，使用选定的和已知的多肽表位 人类免疫缺陷病毒的包膜蛋白，(2)至 在MAP中加入佐剂，以及(3)测试和评估疗效 在动物身上的这些模型。

The overall objective of this project is the design and development of a novel class of human immunodeficiency virus (HIV) vaccines that are synthetic, peptide-based, containing multiple-antigen, carrier-free, and with built-in adjuvant. Such a novel synthetic vaccine is aimed at improving the problems of conjugation, carrier, and adjuvant found in synthetic vaccines. THe proposed design will contain multiple peptide antigens related to HIV such as T helper-inducing determinants and B-cell determinants as well as an adjuvant, all attaching to a small, dendritic branching lysyl core known as the multiple antigen peptide (MAP) system developed recently in our laboratory. Furthermore, the peptide antigens and the lysyl core will be arranged precisely as a single unit and synthesized in a chemically unambiguous manner. In addition, the MAP system contains a high density of peptide antigens on the outer surface (>90% of the total molecular weight) and only a small scaffolding lysyl core (<10% of the molecular weight). These distinct features also serve to overcome the impediment of the carrier problem in the design of peptide-based vaccines. Moreover, the simplicity of the design also provides modifications and developments to enhance both the immunogenicity and long term stability for human vaccines. Finally, fatty acid, liposome-forming or membrane-anchoring moiety conjugated to the MAPs are proposed as suitable models to alleviate the use of adjuvants. Thus, the long term goal of this project is the design and development of a chemical-defined, self-sufficient, multiple-antigen, carrierless, and peptide-based vaccine suitable for humans and protective against human immunodeficiency virus. Although we have demonstrated that the MAP system provides an excellent prototype model in eliciting immunological responses in animals, much of the potentials of the MAP system has yet to be defined. Our immediate goals are (1) to optimize the design of the MAP models, namely; the size, arrangement, stoichiometric relationship of outer peptide antigens and the small branching lysyl core, using selected and known peptide epitopes of the envelop proteins of the human immunodeficiency virus, (2) to incorporate adjuvants in MAPs, and (3) to test and evaluate the efficacy of these models in animals.