Shigellae

病原菌的表面多糖，包括CP或脂多糖（LPS）的O-特异性多糖（OSP），既是重要的毒力因子，也是保护性抗原。这些抗体与医学上有用的蛋白质共价结合形成缀合物，增加了它们的免疫原性，并赋予它们T细胞依赖性，使它们成为适合婴儿和儿童的疫苗。与重组无毒铜绿假单胞菌外蛋白A（rEPA）结合的宋内志贺菌O-SP在暴露于6%至14%发作率的年轻人中显示出超过70%的疗效。这个共轭和S.与琥珀酰化外蛋白A（rEPA-succ）结合的福氏2a是安全的，并在1至4岁儿童中诱导针对同源LPS的IgG抗体。一项在1至4岁儿童中进行的随机、盲法、3期研究表明，这些疫苗是安全的，每种疫苗都作为另一种疫苗的对照。免疫原性和有效性与年龄有关，在1至2岁的儿童中几乎没有有效性，但在3至4岁的儿童中约为70%。如前所述，抗体水平的倍数增加与成人相似，但实际达到的水平较低。 我们已经证明，S。通过其还原端结合到载体蛋白（太阳构型）的1型O-SP比通过几个点连接（晶格构型）结合到蛋白质的天然O-SP的缀合物诱导显著更高的抗体水平。S. Sonnei寡糖没有成功。因此，我们分离了天然O-SP的低分子量O-SP-核心（O-SPC）片段，并使用它们通过还原末端核心的末端Kdo残基与结合BSA或无毒重组白喉毒素或艰难梭菌毒素B的氨氧基接头之间的肟键与蛋白质结合。偶联反应在中性pH、室温和短时间内进行。抗S水平。在年轻远交系小鼠中由这些缀合物诱导的sonnei LPS IgG显著高于由全长O-SP缀合物诱导的那些。 类志贺邻单胞菌O 17的O-SP结构与S. sonnei，但只有S.索尼出版了。我们通过核磁共振（NMR）和质谱研究了类志贺毕赤酵母O 17的核心结构，包括其与O-SP的连接。核心结构，不同于S。Sonnei Core，被分配。

Surface polysaccharides of pathogenic bacteria, including CPs or the O-specific polysaccharide (OSP) of lipopolysaccharides (LPS), function as both essential virulence factors and protective antigens. Covalent binding of these saccharides to medically useful proteins to form conjugates increases their immunogenicity and confers on them T cell dependence, making them suitable vaccines for infants and children. The O-SP of Shigella sonnei bound to recombinant non-toxic P. aeruginosa exoprotein A (rEPA) exhibited an efficacy of over 70 percent in young adults exposed to 6 to 14 percent attack rates. This conjugate and that of S. flexneri 2a bound to the succinylated exoprotein A (rEPA-succ) were safe and induced IgG antibodies to the homologous LPS in 1- to 4-year-olds. A randomized, blinded, Phase 3 study of the conjugates in 1- to 4-year-olds, with each conjugate serving as a control for the other, showed the vaccines to be safe. Immunogenicity and efficacy were age-related with little efficacy in 1- to 2-year-olds but with about 70 percent in 3- to 4-year-olds. As before, fold increases in antibody levels were similar to those for adults, but the actual achieved levels were lower. We have shown that synthetic oligosaccharides of S. dysenteriae type 1 O-SP, bound by their reducing end to a carrier protein (sun configuration), induced significantly higher antibody levels than conjugates of the native O-SP bound to protein by several point attachments (lattice configuration). Synthesis of S. sonnei oligosaccharides was not successful. Therefore, we isolated lowmolecular mass O-SP-core (O-SPC) fragments of the native O-SP and used them to bind to proteins by oxime linkages between the terminal Kdo residues of the reducing end core and the aminoxy linkers bound to either BSA or to non-toxic recombinant diphtheria toxin or C.difficile toxin B. The coupling reaction was performed at a neutral pH, at room temperature, and in a short time. Levels of antiS. sonnei LPS IgG induced by these conjugates in young outbred mice were significantly higher than those induced by the full-length O-SP conjugates. The O-SP of Plesiomonas shigelloides O17 is structurally identical to that of S. sonnei, but only the core structure of S. sonnei has been published. We investigated the core structure of P. shigelloides O17, including its linkage to the O-SP, by nuclear magnetic resonance (NMR) and mass spectroscopy. A core structure, different form the S. sonnei core, was assigned.