ADJUVANT ACTIVITY OF BUTYROLACTONE DRUGS

一种无毒、水溶性、低分子量、 Theracel公司开发的免疫刺激化学组合物 公司将评估其作为疫苗佐剂的效用。 的 丁内酯，包括两类化学成分， 甲基呋喃基丁内酯（MFBLs）和酮基丁内酯（KBLs）将被 在动物模型中测试。 实验设计将用于商业用途 制备的无明矾和含明矾的疫苗[白喉，破伤风， 流感A & B，HIV-1（gp-160/120，p24）]的模型，比较新的 组合物与现有佐剂的组合物。 免疫参数 反应性将包括测定特异性体液和 细胞免疫 由于Theracel的丁内酯是口服活性的， 除了这些，还将评价口服佐剂的概念。 作为疫苗制剂的组分的经典共同施用。 重点将放在选择最佳丁内酯， 增强体液免疫和细胞免疫。 成功完成 第一阶段SBIR将产生新的佐剂组合物， 更广泛和更强烈的免疫反应需要新的基因 工程化的、合成的以及纯化的亚单位疫苗， 弱免疫原性。 新的丁内酯佐剂可能被证明是有用的， 与正在开发的新疫苗联合预防 获得性免疫缺陷综合征（艾滋病）。

A new family of non-toxic, water-soluble, low molecular weight, immunostimulatory, chemical compositions developed by the Theracel Corporation will be assessed for their utility as vaccine adjuvants. The butyrolactones, which include two classes of chemical compositions, the methylfurylbutyrolactones (MFBLs) and ketobutyrolactones (KBLs) are to be tested in animal models. The experimental design will employ commercially prepared alum-free and alum-containing vaccines [diphtheria, tetanus, influenza A & B, HIV-1 (gp-160/120, p24)] in model which compares the new compositions with current adjuvants. The parameters for immune responsiveness will include assays to measure both specific humoral and cell-mediated immunity. Since Theracel's butyrolactones are orally active, the concept of an oral adjuvant will be evaluated in addition to the classical co-administration as a constituent of the vaccine preparation. Emphasis will be placed on selection of the optimum butyrolactone which can augment both humoral and cell-mediated immunity. Successful completion of the phase I SBIR will yield a new adjuvant composition that will produce the broader and more intense immune response needed for newer genetically engineered, synthetic, as well as purified subunit vaccines which are often weakly immunogenic. The new butyrolactone adjuvant may prove useful in combination with new vaccines under development for the prevention of Acquired Immune Deficiency syndrome (AIDS).