VACCINE ADJUVANTS FOR AIDS

该项目的总体目标是设计和开发一个 一类新的人类免疫缺陷病毒（HIV）疫苗， 合成的、基于肽的、含有多种抗原的、无载体的，以及 与内置佐剂。 这种新型合成疫苗旨在 改善了在本发明中发现的缀合、载体和佐剂的问题， 合成疫苗 所提出的设计将包含多个肽 与HIV相关的抗原，如T辅助细胞诱导决定簇和B细胞 决定簇以及佐剂，都附着在一个小的树突状细胞上， 称为多抗原肽（MAP）系统的分支赖氨酰核心 最近在我们的实验室里发现的。 此外，肽抗原 赖氨酰核将被精确地排列为单个单元， 以化学上明确的方式合成。 此外，MAP 系统在外表面上含有高密度的肽抗原 （>90%的总分子量）和只有一个小的支架赖氨酰 核心（<10%的分子量）。 这些独特的特征也有助于 为了克服设计中载体问题的障碍， 基于肽的疫苗 此外，设计的简单性还 提供修改和开发，以增强 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， 地图被建议作为适当的模式，以减轻使用 佐剂 因此，该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，多抗原的， 无载体和基于肽的疫苗， 人类免疫缺陷病毒。 虽然我们已经证明MAP系统提供了一个很好的 原型模型在引发动物的免疫反应，大部分 MAP系统的潜力还有待确定。 我们眼前的 目标是（1）优化MAP模型的设计，即：尺寸， 排列，外肽抗原的化学计量关系， 小分支赖氨酰核心，使用选择的和已知的肽表位 在人类免疫缺陷病毒的包膜蛋白中，（2）至 在MAP中掺入佐剂，和（3）测试和评估功效 这些动物模型。

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.