Alving C R, Richards R L, Moss J, Alving L I, Clements J D, Shiba T, Kotani S, Wirtz R A, Hockmeyer W T
Vaccine. 1986 Sep;4(3):166-72. doi: 10.1016/0264-410x(86)90005-8.
Two antigens, cholera toxin (CT) and a synthetic albumin-conjugated 16-residue peptide derived from the circumsporozoite (CS) protein of Plasmodium falciparum sporozoites, were tested as immunogens in rabbits. The malaria peptide-albumin conjugate by itself was completely nonimmunogenic, and although cholera toxin was immunogenic it also expressed considerable native toxicity. After attachment of CT to liposomes containing ganglioside GM1, toxicity of CT was completely eliminated and antigenicity was enhanced. Therefore liposomes may be capable of reducing toxicity of certain potentially dangerous antigens such as toxins. After incorporation of the malaria peptide-albumin conjugate into liposomes a high titre of specific antibodies was induced against the malaria peptide but not against albumin. These antibodies also reacted with native CS protein. Three adjuvants, including lipid A and two types of lipophilic muramyl dipeptide, were compared and found to be effective in liposomes. Based on the conversion of synthetic P. falciparum CS peptide from a nonimmunogenic to an immunogenic form and on the 'toxoiding' effect of liposomes for CT, it is concluded that liposomes should be considered as being a useful carrier for antigens and adjuvants for vaccines for poorly antigenic or toxic substances.
两种抗原，霍乱毒素（CT）和一种源自恶性疟原虫子孢子环子孢子（CS）蛋白的合成白蛋白偶联16肽，在兔体内作为免疫原进行了测试。疟疾肽-白蛋白偶联物本身完全无免疫原性，虽然霍乱毒素具有免疫原性，但也表现出相当大的天然毒性。将CT附着于含有神经节苷脂GM1的脂质体后，CT的毒性完全消除，抗原性增强。因此，脂质体可能能够降低某些潜在危险抗原（如毒素）的毒性。将疟疾肽-白蛋白偶联物掺入脂质体后，诱导产生了针对疟疾肽而非白蛋白的高滴度特异性抗体。这些抗体也与天然CS蛋白发生反应。比较了三种佐剂，包括脂多糖A和两种亲脂性胞壁酰二肽，发现它们在脂质体中有效。基于合成的恶性疟原虫CS肽从无免疫原性形式转变为免疫原性形式以及脂质体对CT的“类毒素化”作用，得出结论，脂质体应被视为一种有用的载体，用于承载抗原和佐剂，以制备针对低抗原性或有毒物质的疫苗。
