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首页> 外文期刊>Infection and immunity >Preparation, characterization, and immunogenicity of meningococcal immunotype L2 and L3,7,9 phosphoethanolamine group-containing oligosaccharide-protein conjugates.
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Preparation, characterization, and immunogenicity of meningococcal immunotype L2 and L3,7,9 phosphoethanolamine group-containing oligosaccharide-protein conjugates.

机译：脑膜炎球菌免疫型L2和L3,7,9含磷酸乙醇胺基的寡糖-蛋白质偶联物的制备，表征和免疫原性。

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摘要

A method was developed for the well-defined coupling of phosphoethanolamine group (PEA)- and carboxylic acid group-containing polysaccharides and oligosaccharides to proteins without the need for extensive modification of the carbohydrate antigens. The carboxylic acid group of the terminal 2-keto-3-deoxyoctulosonic acid moiety was utilized to introduce a thiol function in meningococcal immunotype L2 and L3,7,9 lipopolysaccharide-derived oligosaccharides. The thiol group-containing oligosaccharides were subsequently coupled to bromoacetylated proteins. Immunotype L2 and L3,7,9 PEA group-containing oligosaccharide-tetanus toxoid conjugates were prepared, and their immunogenicities were studied in rabbits. Both the immunotype L2 and immunotype L3,7,9 conjugates evoked high immunoglobulin G (IgG) antibody titers after the first booster injection. These conjugates also displayed an ability to induce long-lasting IgG antibody levels which could be detected until 9 months after one booster injection at week 3. The adjuvant Quil A enhanced the immune response to all the conjugates to a minor extent, which is in contrast with reported adjuvant effects of Quil A on these types of antigens in mice. A conjugate prepared from the dephosphorylated L3,7,9 oligosaccharides evoked a significantly lower IgG response than a similar PEA-containing conjugate, and enzyme-linked immunosorbent assay inhibition studies indicated a different epitope specificity. Furthermore, antisera elicited with the complete bacteria contained antibodies directed against PEA-containing epitopes, which stresses the importance of the presence of unmodified PEA groups in meningococcal lipopolysaccharide-derived oligosaccharide-protein conjugates. The procedure developed offers an elegant solution for the specific coupling of meningococcal PEA-containing oligosaccharides to proteins and may therefore be a very useful tool in the development of a vaccine against group B meningococci.
机译：开发了一种方法，用于将含磷酸乙醇胺基团（PEA）和含羧酸基团的多糖和寡糖与蛋白质明确偶联，而无需对碳水化合物抗原进行大量修饰。末端2-酮-3-脱氧辛二酸部分的羧酸基团被用于在脑膜炎球菌免疫型L2和L3,7,9脂多糖衍生的寡糖中引入硫醇功能。随后将含硫醇基的寡糖与溴乙酰化的蛋白质偶联。制备了免疫型L2和L3、7、9 PEA基团的寡糖-破伤风类毒素缀合物，并在兔中研究了它们的免疫原性。第一次加强注射后，免疫型L2和免疫型L3,7,9缀合物均引起高免疫球蛋白G（IgG）抗体效价。这些缀合物还显示出能够诱导持久的IgG抗体水平的能力，直到第3周一次加强注射后9个月，这种水平才能被检测到。佐剂Quil A在较小程度上增强了对所有缀合物的免疫反应，相比之下报道了Quil A对小鼠中这些类型抗原的佐剂作用。由脱磷酸的L3,7,9寡糖制备的缀合物引起的IgG应答比类似的含PEA的缀合物低得多，并且酶联免疫吸附试验抑制研究表明不同的表位特异性。此外，由完整细菌引起的抗血清包含针对含PEA抗原决定簇的抗体，这强调了在脑膜炎球菌脂多糖衍生的寡糖-蛋白质缀合物中存在未修饰的PEA基团的重要性。所开发的方法为含脑膜炎球菌PEA的寡糖与蛋白质的特异性偶联提供了一种优雅的解决方案，因此可能是开发针对B组脑膜炎球菌的疫苗的非常有用的工具。

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