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首页> 外文期刊>Infection and immunity >Synthesis and physicochemical and immunological characterization of pneumococcus type 12F polysaccharide-diphtheria toxoid conjugates.
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Synthesis and physicochemical and immunological characterization of pneumococcus type 12F polysaccharide-diphtheria toxoid conjugates.

机译：肺炎球菌12F型多糖-白喉类毒素缀合物的合成及其理化和免疫学表征。

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摘要

A scheme for the synthesis and purification of conjugates, composed of the type 12F capsular polysaccharide of Streptococcus pneumoniae (Pn12F) and diphtheria toxoid, is described. The scheme is a modification of that described previously for the Vi capsular polysaccharide of Salmonella typhi, a linear homopolymer of N-acetylgalactoseaminouronic acid (S. C. Szu, A. L. Stone, J. D. Robbins, R. Schneerson, and J. B. Robbins, J. Exp. Med. 166:1510-1524, 1986). Pn12F is a branched-chain copolymer composed of a hexasaccharide repeating unit containing an aminouronic acid, N-acetylmannoseaminouronic acid (K. Leontein, B. Lindberg, and J. Lonngren, Can. J. Chem. 59:2081-2085, 1981). Sulfhydryl groups were introduced into Pn12F by forming an amide bond between cystamine and carboxyl groups of N-acetylmannoseaminouronic acid in the presence of a carbodiimide. The disulfide moiety of cystamine was reduced to form the cysteamine derivative of Pn12F which was, in turn, covalently bound to diphtheria toxoid by using the heterobifunctional linker N-succinimidyl-3-(2-pyridylthio)propionate. Unbound, high-molecular-weight Pn12F was removed from the conjugate by hydrophobic interaction chromatography through octyl Sepharose by using n-octyl-beta-D-glucopyranoside as the eluent. In young outbred mice, Pn12F did not elicit detectable serum antibodies. Pn12F-diphtheria toxoid, in contrast, elicited antibodies after two injections and had T-cell-dependent properties as evidenced by a response to priming and by its ability to elicit booster responses. This scheme seems applicable to the synthesis of conjugates with other capsular polysaccharides containing aminouronic acids. Clinical evaluation of Pn12F-diphtheria toxoid conjugates in healthy and in immunocompromised hosts is planned.
机译：描述了由肺炎链球菌（Pn12F）的12F型荚膜多糖和白喉类毒素组成的结合物的合成和纯化方法。该方案是先前对伤寒沙门氏菌的荚膜多糖（N-乙酰半乳糖氨基糖醛酸的线性均聚物（SC Szu，AL Stone，JD Robbins，R.Schneerson和JB Robbins，J.Exp.Med。 166：1510-1524，1986）。 Pn12F是由含有氨基糖醛酸，N-乙酰甘露糖基氨基糖醛酸的六糖重复单元组成的支链共聚物（K.Leontein，B.Lindberg和J.Lonngren，Can.J.Chem.59：2081-2085，1981） 。在碳二亚胺的存在下，通过在N-乙酰基甘露糖氨基糖醛酸的胱胺和羧基之间形成酰胺键，将巯基引入Pn12F中。胱胺的二硫键部分还原形成Pn12F的胱胺衍生物，然后通过使用异双功能接头N-琥珀酰亚胺基-3-（2-吡啶硫基）丙酸酯共价结合白喉类毒素。使用正辛基-β-D-吡喃葡萄糖苷作为洗脱液，通过辛基琼脂糖通过疏水相互作用色谱从结合物中除去未结合的高分子量Pn12F。在年轻的近交小鼠中，Pn12F不会引起可检测的血清抗体。相比之下，Pn12F-白喉类毒素在两次注射后会引发抗体，并具有T细胞依赖性特性，这由对引发的反应及其引发加强反应的能力证明。该方案似乎适用于与含有氨基糖醛酸的其他荚膜多糖的缀合物的合成。计划在健康和免疫功能低下的宿主中对Pn12F-白喉类毒素缀合物进行临床评估。

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