Pinto Vittoria, Berti Francesco
Novartis Vaccines, Via Fiorentina 1, I-53100 Siena, Italy.
Novartis Vaccines, Via Fiorentina 1, I-53100 Siena, Italy.
J Pharm Biomed Anal. 2014 Sep;98:9-15. doi: 10.1016/j.jpba.2014.05.004. Epub 2014 May 13.
Carbohydrate-based vaccines constitute a potent tool for prevention of life-threatening bacterial infectious diseases like meningitis and pneumonia. Group B Streptococcus (GBS) is a major cause of neonatal sepsis and meningitis, particularly in infants born from mothers carrying the bacteria, and no vaccine is currently available. High-field Nuclear Magnetic Resonance (NMR) spectroscopy has been found to be an extremely robust tool for tracking the industrial process manufacturing of carbohydrate-based vaccines. Here we review the differences in the repeating unit structures of GBS capsular polysaccharide (CPS) type (Ia, Ib, II-VIII) yielding unique NMR proton profiles. All the profiles provided opportunities for selecting well resolved signals, in particular in the anomeric, the methylene protons at position C3 of N-acetyl-neuraminic acid (NeupNAc) and the N-Acetyl regions, which could be employed to develop an identity assay for monovalent vaccine bulks. Finally we reported a preliminary proof of concept of identity testing on a GBS CPS type Ia, Ib, III trivalent vaccine as blended bulks, based on the selection of one specific signal for each type in the anomeric region.
基于碳水化合物的疫苗是预防如脑膜炎和肺炎等危及生命的细菌性传染病的有力工具。B族链球菌(GBS)是新生儿败血症和脑膜炎的主要病因,尤其是在母亲携带该细菌所生的婴儿中,目前尚无疫苗可用。高场核磁共振(NMR)光谱已被证明是跟踪基于碳水化合物的疫苗工业生产过程的极其强大的工具。在此,我们综述了GBS荚膜多糖(CPS)各型(Ia、Ib、II - VIII)重复单元结构的差异,这些差异产生了独特的NMR质子谱。所有这些谱图都为选择分辨率良好的信号提供了机会,特别是在异头物、N - 乙酰神经氨酸(NeupNAc)C3位的亚甲基质子以及N - 乙酰区域,这些信号可用于开发单价疫苗原液的鉴别检测方法。最后,我们报告了基于在异头物区域为每种类型选择一个特定信号,对GBS CPS Ia、Ib、III三价疫苗混合原液进行鉴别测试的初步概念验证。