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A 群和 X 群脑膜炎奈瑟菌多糖的相对稳定性。

Relative stability of meningococcal serogroup A and X polysaccharides.

机构信息

Novartis Vaccines, Via Fiorentina 1, I-53100 Siena, Italy.

出版信息

Vaccine. 2012 Oct 5;30(45):6409-15. doi: 10.1016/j.vaccine.2012.08.021. Epub 2012 Aug 22.

Abstract

Prior to the introduction of the MenAfriVac™ serogroup A glycoconjugate vaccine in September 2010, serogroup A was the major epidemic disease-causing meningococcal serogroup in the African meningitis belt. However, recently serogroup X meningococcal (MenX) disease has received increased attention because of outbreaks recorded in this region, with increased endemic levels of MenX disease over the past 2 years. Whereas polysaccharide-protein conjugate vaccines against meningococcal serogroups A, C, W and Y (MenA, MenC, MenW, MenY) are on the market, a vaccine able to protect against MenX has never been achieved. The structure of serogroup A, C, W and Y meningococcal polysaccharides has been already fully elucidated by NMR. MenX capsular polysaccharide (MenX CPS) structure is also documented but fewer characterization data have been published. We have applied here (1)H NMR, (31)P NMR and HPLC to evaluate the stability of MenX CPS in aqueous solution as compared to MenA capsular polysaccharide (MenA CPS). The stability study demonstrated that MenA CPS is more susceptible to hydrolytic degradation than MenX CPS. The different stereochemistry of the N-acetyl group at position C(2) of mannosamine (MenA CPS) and glucosamine (MenX CPS) respectively might play a fundamental role in this susceptibility to polysaccharide chain degradation. The satisfactory stability of MenX CPS predicts the possibility that a stable fully-liquid MenX polysaccharide or glycoconjugate vaccine could be developed.

摘要

在 2010 年 9 月 MenAfriVac™A 群脑膜炎球菌荚膜多糖结合疫苗推出之前,A 群是非洲脑膜炎带中主要的流行疾病脑膜炎奈瑟菌血清群。然而,最近 X 群脑膜炎奈瑟菌(MenX)疾病引起了更多的关注,因为该地区记录了疫情爆发,过去 2 年中 MenX 疾病的地方性流行水平有所增加。虽然有针对脑膜炎奈瑟菌血清群 A、C、W 和 Y(MenA、MenC、MenW、MenY)的多糖-蛋白结合疫苗上市,但从未开发出能够预防 MenX 的疫苗。A、C、W 和 Y 群脑膜炎奈瑟菌多糖的结构已经通过 NMR 得到充分阐明。MenX 荚膜多糖(MenX CPS)的结构也有记录,但发表的特征化数据较少。我们在这里应用(1)H NMR、(31)P NMR 和 HPLC 来评估 MenX CPS 在水溶液中的稳定性,与 MenA 荚膜多糖(MenA CPS)进行比较。稳定性研究表明,MenA CPS 比 MenX CPS 更容易发生水解降解。甘露糖胺(MenA CPS)和葡萄糖胺(MenX CPS)位 C(2)上的 N-乙酰基的不同立体化学结构可能在这种对多糖链降解的敏感性中发挥了根本作用。MenX CPS 的良好稳定性预示着可能开发出稳定的全液体 MenX 多糖或糖缀合物疫苗。

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