ADJUVANTICITY OF STEARYL-TYROSINE--SUBUNIT & HIV SYSTEM

硬脂酰酪氨酸(ST)是一种天然存在的饱和脂肪醇 用自然产生的氨基酸酯化的。它有能力 吸附抗原，然后慢慢释放。初步研究表明， ST状明矾可增强免疫反应。将ST用作佐剂可 代表一个优势，因为它没有观察到的副作用 明矾、长链乙胺类物质及其他助剂的情况。 在过去的两年里，有证据表明 硬脂酰酪氨酸是一种稳定安全的合成化合物，具有广泛的应用前景。 与明矾相比，明胶具有更强的佐剂活性 破伤风类毒素、脊髓灰质炎病毒疫苗引起的抗体反应 乙肝表面抗原和两个来源于 HIV gpl2O蛋白。各种毒性试验表明，该化合物是- 安然无恙。本项目的主要目标是评价佐剂活性。 硬脂酰酪氨酸，这似乎是可以接受的人类使用。 我们建议的具体目的如下：1.研究 ST增强对多种抗原的抗体应答。这些 研究将包括代表发育的原型的抗原。 新一代疫苗往往是免疫力较差的疫苗，如 亚单位疫苗。合成肽和独特型疫苗。2.学习 ST佐剂对免疫猕猴抗体应答的影响 与gp160携带的四个表位相对应的合成肽 HIV病毒的包膜蛋白。3.研究ST对细胞的影响 HIV gpl2O蛋白或人工合成蛋白诱导的免疫应答 多肽。 4.研究ST的免疫原性副反应和免疫反应。 激活自体反应克隆。5.开发新的自然发生的 氨基酸的脂肪醇衍生物，目标是建立一种 新的衍生物具有更强的佐剂性和无副作用。 这个项目的最终目标是开发一种佐剂，它是 适合人类接种HIV疫苗。

Stearyl-tyrosine (ST) is a naturally occuriring saturated fatty alcohol esterified with a naturally occurring amino acid. It has the capacity to adsorb antigen and release it slowly. Preliminary studies have shown that ST like alum can enhance immune responses. Usage of ST as an adjuvant may represent an advantage since, it lacks the side effects observed in the case of Alum, long chain ethyl amine substances and other adjuvants. During the past two years evidence has been provided that stearyl-tyrosine is a stable and safe synthetic compound exhibiting a stronger adjuvant activity than Alum ith respect to the enhancement of antibody response elicited by tetanus toxoid, poliovirus vaccine, hepatitis B surface antigen and two synthetic peptides derived from the HIV gpl2O protein. Various toxicity tests showed that this compound is - safe. The major goal of this project is to evaluate the adjuvant activity of stearyl-tyrosine which appears to be acceptable for human use. The specific aims of our proposal are as follows: 1. To study the enhancement of antibody response against various antigens by ST. These studies will include antigens representing a protatype for the development of new generation of vaccines which tend to be poor immunagens such as subunit vaccines. synthetic peptides and idiotype vaccines. 2. To study the effect of ST adjuvant on the antibody response in monkeys immunized with synthetic peptides corresponding to four epitopes borne by gp160 envelope protein of HIV virus. 3.To study the effect of ST on cell mediated immune response elicited by HIV gpl2O protein or synthetic peptides. 4. To study the side effects of ST with respect to immunogenicity and the activation of autoreactive clones. 5. To develop new naturally occurring fatty alcohol derivatives of amino acids with the goal of establishing a new derivative having stronger adjuvanticity and devoid of side effects. The ultimate goal of this project is to develop an adjuvant which is suitable for human use in the vaccination against HIV.rr