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 用天然存在的氨基酸酯化。它有能力 吸附抗原并缓慢释放。初步研究表明， ST像明矾可以增强免疫反应。ST作为佐剂的用途可 代表一个优点，因为它没有在实验中观察到的副作用。 如明矾、长链乙胺类物质及其它助剂。 在过去两年中，有证据表明， 硬脂酰-酪氨酸是一种稳定和安全的合成化合物， 比明矾更强的佐剂活性 破伤风类毒素，脊髓灰质炎病毒疫苗， B型肝炎表面抗原和两种合成肽 HIV gp 120蛋白。各种毒性试验表明，这种化合物是- 安全了本项目的主要目标是评价佐剂活性 硬脂酰-酪氨酸，这似乎是人类使用可接受的。 我们建议的具体目标如下：1。研究 通过ST增强针对各种抗原的抗体应答。 研究将包括代表一种原型的抗原， 新一代疫苗的免疫力往往很差， 亚单位疫苗合成肽和独特型疫苗。2.研究 ST佐剂对免疫猴抗体应答的影响 用对应于GP 160携带的四个表位的合成肽 HIV包膜蛋白。3.研究ST对细胞增殖的影响， 由HIV gpl 20蛋白或合成的 缩氨酸 4.研究ST在免疫原性和免疫耐受性方面的副作用。 自身反应性克隆的激活。5.开发新的自然发生的 氨基酸的脂肪醇衍生物，目的是建立一种 具有更强的佐剂性和无副作用的新衍生物。 该项目的最终目标是开发一种佐剂， 适用于人类接种HIV疫苗。rr

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