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Versatile and efficient synthesis of protein-polysaccharide conjugate vaccines using aminooxy reagents and oxime chemistry

机译:使用氨氧基试剂和肟化学多功能高效合成蛋白-多糖结合疫苗

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摘要

Applications of oxime chemistry are described for the efficient bioconjugation of proteins and polysaccharides for the preparation of conjugate vaccines. A number of approaches are described in this manuscript to functionalize proteins and polysaccharides with aminooxy (AO) groups and aldehydes which could then be covalently linked to each other via oxime formation, without the need for reduction. By using limiting numbers of active groups on each component, the extent of inter- and intramolecular crosslinking could be controlled. The approaches described are compatible and complementary to a number of chemistries currently used in conjugate vaccine synthesis. Oxime chemistry can be used to both simplify the synthesis of and increase yields of conjugate vaccines. Mice immunized with pneumococcal type 14 conjugates that were made using oxime chemistry mounted significant anti-polysaccharide immune responses. The primary immune response could be boosted, indicating that the polysaccharide conjugate had characteristics of a T cell dependent antigen.
机译:描述了肟化学在蛋白质和多糖的有效生物缀合以制备结合疫苗中的应用。本手稿中描述了许多方法,可对具有氨基氧基(AO)基团和醛基的蛋白质和多糖进行功能化,然后可以通过肟的形成将它们彼此共价连接,而无需还原。通过在每个组分上使用有限数量的活性基团,可以控制分子间和分子内交联的程度。所描述的方法与目前在缀合物疫苗合成中使用的许多化学方法兼容并互补。肟化学可用于简化缀合疫苗的合成并提高其产量。用肟化学制备的用肺炎球菌14型结合物免疫的小鼠表现出明显的抗多糖免疫反应。可以增强初次免疫反应,表明多糖结合物具有T细胞依赖性抗原的特征。

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