Estevez F, Carr A, Solorzano L, Valiente O, Mesa C, Barroso O, Sierra G V, Fernandez L E
Finlay Institute, C. de La Habana, Cuba.
Vaccine. 1999 Aug 20;18(1-2):190-7. doi: 10.1016/s0264-410x(99)00219-4.
Certain gangliosides are tumor-associated antigens that constitute potential targets for cancer immunotherapy. A major drawback in the design of ganglioside-based cancer vaccines, however, is the poor immunogenicity of these glycolipids. Here we report the immunological and physicochemical properties of very small size proteoliposomes (VSSP) obtained by using anionic detergents to incorporate gangliosides into the outer membrane protein complex (OMPC) of N. meningitidis. VSSP of three different gangliosides, GM3, NGcGM3 and GD3, were tested. These gangliosides differ in level of expression in normal tissues and in immunogenicity in different animal species. We show that the immunization with VSSP in an oil adjuvant consistently induced both IgM and IgG anti-ganglioside antibodies. In the mouse, the anti-ganglioside IgG fraction was not restricted to the typical T-independent isotype IgG3. Unexpectedly, significant levels of the T-dependent IgG1, IgG2a and particularly IgG2b were also found. VSSP-mediated enhancement of the immunogenicity was not restricted to the relatively immunogenic ganglioside GD3, satisfactory immune responses against highly tolerated GM3 and NGcGM3 were also obtained. Similar results were achieved in chickens and monkeys. No reactogenicity was observed even when self-gangliosides were used for immunization. VSSP overcame natural tolerance to gangliosides in an adjuvant dependent fashion.
某些神经节苷脂是肿瘤相关抗原，构成癌症免疫治疗的潜在靶点。然而，基于神经节苷脂的癌症疫苗设计中的一个主要缺点是这些糖脂的免疫原性较差。在这里，我们报告了通过使用阴离子洗涤剂将神经节苷脂掺入脑膜炎奈瑟菌的外膜蛋白复合物（OMPC）中获得的非常小尺寸的蛋白脂质体（VSSP）的免疫学和物理化学性质。测试了三种不同神经节苷脂GM3、NGcGM3和GD3的VSSP。这些神经节苷脂在正常组织中的表达水平以及在不同动物物种中的免疫原性存在差异。我们表明，在油佐剂中用VSSP免疫始终诱导IgM和IgG抗神经节苷脂抗体。在小鼠中，抗神经节苷脂IgG部分不限于典型的非T细胞依赖性同种型IgG3。出乎意料的是，还发现了显著水平的T细胞依赖性IgG1、IgG2a，尤其是IgG2b。VSSP介导的免疫原性增强不仅限于相对具有免疫原性的神经节苷脂GD3，还获得了针对高度耐受性GM3和NGcGM3的令人满意的免疫反应。在鸡和猴子中也取得了类似的结果。即使使用自身神经节苷脂进行免疫，也未观察到反应原性。VSSP以佐剂依赖性方式克服了对神经节苷脂的天然耐受性。
