Synthesis and some immunologic properties of an O-acetyl pectin [poly(1-->4)-alpha-D-GalpA]-protein conjugate as a vaccine for typhoid fever
Synthesis and some immunologic properties of an O-acetyl pectin [poly(1-->4)-alpha-D-GalpA]-protein conjugate as a vaccine for typhoid fever
复制标题
O-乙酰果胶 [poly(1-->4)-alpha-D-GalpA]-蛋白缀合物作为伤寒疫苗的合成和一些免疫学特性
作者：
S. Szu;S. Bystrický;M. Hinojosa;W. Egan;J. Robbins
果胶是一种植物多糖，主要是聚(1-->4)-α-D-GalpA的线性均聚物，中性糖含量<5%：其分子大小在400 kDa左右分布较宽，酯化度<5%。伤寒沙门氏菌 (Vi) 荚膜多糖的结构与果胶的不同之处在于，它在 C-2 处被 N 乙酰化，在 C-3 处被 O 乙酰化，分子大小约为 2 x 10(3) kDa。果胶和Vi之间不存在血清学交叉反应。当 O 在 C-2 和 C-3 处乙酰化时，果胶在双重免疫扩散中与 Vi 具有抗原性相同。与 Vi 不同，O-乙酰化果胶 (OAcPec) 在小鼠中不具有免疫原性，可能是因为其分子量相对较低。在3至8℃下储存3个月后，OAcPec的O-乙酰基含量或M(r)没有变化。在 60 摄氏度时，OAcPec 的 M(r) 下降得比 Vi 更快。 OAcPec 与破伤风类毒素缀合可在小鼠体内引发 Vi 抗体，重新注射可引发加强反应。 OAcPec-破伤风类毒素缀合物引起的 Vi 抗体水平低于 Vi 缀合物引起的 Vi 抗体水平，但这些差异不具有统计学显着性。 OAcPec 具有一些优点，因为它可以通过标准化比色测定进行测量，并且因为它与蛋白质形成比 Vi 更可溶的缀合物。一个缺点是它的糖苷键不像Vi那样稳定。使用植物多糖果胶作为免疫原来预防由荚膜病原体（伤寒沙门氏菌）引起的全身感染，为改善多糖疫苗的制备和免疫原性提供了一种新方法。
Pectin, a plant polysaccharide, is mostly a linear homopolymer of poly(1-->4)-alpha-D-GalpA with < 5% neutral sugars: its molecular size has a broad distribution around 400 kDa, and the degree of esterification is < 5%. The structure of the capsular polysaccharide of Salmonella typhi (Vi) differs from pectin in that it is N acetylated at C-2 and O acetylated at C-3, and has a molecular size of approximately 2 x 10(3) kDa. There is no serological cross-reaction between pectin and Vi. Pectin, when O acetylated at C-2 and C-3, is antigenically identical to Vi in double immunodiffusion. Unlike Vi, O-acetylated pectin (OAcPec) is not immunogenic in mice, probably because of its comparatively low molecular weight. After storage at 3 to 8 degrees C for 3 months, there was no change in the O-acetyl content or the M(r) of OAcPec. At 60 degrees C, the M(r) of OAcPec declined more rapidly than that of Vi. OAcPec conjugated to tetanus toxoid elicited Vi antibodies in mice, and reinjection elicited a booster response. The levels of Vi antibodies elicited by OAcPec-tetanus toxoid conjugates were lower than those elicited by Vi conjugates, but these differences were not statistically significant. OAcPec has some advantages because it can be measured by standardized colorimetric assays and because it forms more soluble conjugates with proteins than does Vi. One disadvantage is that its glycosidic bond is not as stable as that of Vi. The use of a plant polysaccharide, pectin, as an immunogen for prevention of a systemic infection caused by a capsulated pathogen (S. typhi) provides a novel approach to improve the preparation and immunogenicity of polysaccharide-based vaccines.