Kensil C R, Wu J Y, Anderson C A, Wheeler D A, Amsden J
Aquila Biopharmaceuticals, Inc., Worcester, MA, USA.
Dev Biol Stand. 1998;92:41-7.
QS-21 and QS-7 are two adjuvant-active saponins that can be obtained in high purity from Quillaja saponaria Molina extracts. QS-21 is a highly characterized compound and is known to be a potent adjuvant for antibody and CD8+ CTL response to subunit antigens. Less is known about the activity and structure of the hydrophilic saponin QS-7. Hence, we have carried out a detailed structural and immunological characterization. As with QS-21, QS-7 was shown to be a 3,28-O-bisglycoside quillaic acid, with some differences being a higher degree of glycosylation and a considerably shorter fatty acyl unit in QS-7. These differences were correlated to a lower lytic activity against sheep red blood cells. Different doses of QS-7 were evaluated for stimulation of immune response to the antigen ovalbumin, given three times by subcutaneous route to C57BL/6 mice. QS-7 doses of 40 micrograms or higher were shown to induce a strong CD8+ CTL response reproducibly against E. G7-OVA targets (similar to that induced by a 5-10 micrograms dose of QS-21). QS-7 (at doses above 5 micrograms) was also shown to stimulate CTL against peptide 18 of HIV-1IIIB gp120 after three immunizations of Balb/c mice with recombinant gp120 and different doses of QS-7. These data suggest that a hydrophilic saponin with low lytic activity can stimulate MHC Class I CTL responses although a higher minimum dose may be required for some antigens.
QS - 21和QS - 7是两种具有佐剂活性的皂苷,可从皂树(Quillaja saponaria Molina)提取物中高纯度获得。QS - 21是一种特征明确的化合物,已知是一种有效的佐剂,可促进针对亚单位抗原的抗体和CD8 + CTL反应。关于亲水性皂苷QS - 7的活性和结构了解较少。因此,我们进行了详细的结构和免疫学表征。与QS - 21一样,QS - 7被证明是一种3,28 - O - 双糖苷基奎诺酸,不同之处在于QS - 7的糖基化程度更高,脂肪酰基单元明显更短。这些差异与对绵羊红细胞的较低溶血活性相关。评估了不同剂量的QS - 7对卵清蛋白抗原免疫反应的刺激作用,通过皮下途径给C57BL / 6小鼠注射三次。结果显示,40微克或更高剂量的QS - 7可重复诱导针对E.G7 - OVA靶标的强烈CD8 + CTL反应(类似于5 - 10微克剂量的QS - 21所诱导的反应)。在用重组gp120和不同剂量的QS - 7对Balb / c小鼠进行三次免疫后,QS - 7(剂量高于5微克)也被证明可刺激针对HIV - 1IIIB gp120肽18的CTL反应。这些数据表明,一种具有低溶血活性的亲水性皂苷可以刺激MHC I类CTL反应,尽管某些抗原可能需要更高的最小剂量。