Antigenicity of dextran-protein conjugates in mice. Effect of molecular weight of the carbohydrate and comparison of two modes of coupling.

Antigenicity of dextran-protein conjugates in mice. Effect of molecular weight of the carbohydrate and comparison of two modes of coupling.
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DOI:
10.4049/jimmunol.143.4.1259
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发表时间:
1989-08
影响因子:
4.4
通讯作者:
Ilkka Seppälä;O. Mäkelä
Ilkka Seppälä;O. Mäkelä
中科院分区:
医学2区
文献类型:
--
作者:
Ilkka Seppälä;O. Mäkelä

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多糖或其分解产物的蛋白质缀合物被用作改进的“T依赖性”疫苗。我们试图通过测试 α1-6 葡聚糖和鸡血清白蛋白的 13 种结合物(BALB/c 和 CBA)在小鼠体内的免疫原性来确定未来结合疫苗的最佳特性。所有缀合物均诱导比多糖更强的抗葡聚糖抗体反应,并且这些抗体中有相当一部分是 IgG。然而,存在一系列抗原性。使用携带小葡聚糖分子(分子量 1000 至 4000)通过还原端与蛋白质偶联的缀合物获得了一致的强烈反应。通过将糖的大小增加到40,000 Da,或通过允许糖分子多次附着到蛋白质上,对这种“最佳”缀合物进行修饰,降低了其抗原性。碳水化合物/蛋白质比率从 0.17 到 0.49 不等,与优异的抗葡聚糖反应相关。
Protein conjugates of polysaccharides or their breakdown products are being used as improved "T-dependent" vaccines. We tried to define optimal characteristics of future conjugate vaccines by testing the immunogenicity of thirteen conjugates of alpha 1-6 dextran and chicken serum albumin in mice (BALB/c and CBA). All conjugates induced stronger antidextran antibody responses than the polysaccharide, and a fair proportion of these antibodies were IgG. However, there was a range of antigenicities. Consistently strong responses were obtained with conjugates that carried small dextran molecules (m.w. 1000 to 4000) coupled to the protein via the reducing end. Modification of such an "optimal" conjugate either by increasing the size of the saccharide to 40,000 Da, or by permitting multiple attachments of the saccharide molecule to the protein, reduced its antigenicity. Carbohydrate/protein ratios varying from 0.17 to 0.49 were associated with excellent antidextran responses.