Process development and immunogenicity studies on a serogroup 'X' Meningococcal polysaccharide conjugate vaccine

被引:18
作者
Chilukuri, Srinivas Reddy [1 ]
Reddy, Peddi [1 ]
Avalaskar, Nikhil [1 ]
Mallya, Asha [1 ]
Pisal, Sambhaji [1 ]
Dhere, Rajeev M. [1 ]
机构
[1] Serum Inst India Ltd, Dept Res & Dev, Pune 411028, Maharashtra, India
关键词
Meningococcal group X; Capsular polysaccharide; Lipopolysaccharide; Serum bactericidal assay titer; Tetanus toxoid; High performance liquid chromatography - size exclusion chromatography (HPLC-SEC); NUCLEAR-MAGNETIC-RESONANCE; NEISSERIA-MENINGITIDIS; CAPSULAR POLYSACCHARIDE; LIQUID-CHROMATOGRAPHY; CHEMISTRY;
D O I
10.1016/j.biologicals.2013.12.001
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
Meningococcal group X (MenX) is responsible for recent outbreaks of meningitis reported in sub-Saharan region of Africa. Although protective vaccines are available for meningitis, they are not effective against MenX. An efficacious, monovalent conjugate vaccine was designed against MenX and a fed-batch fermentation process was developed. The MenX polysaccharide (PS) was purified and yield estimated to be 15-fold higher than the reported elsewhere. Structure of MenX polysaccharide was confirmed by H-1, C-13 NMR spectroscopy analysis. Molecular weight of PS was found to be 310 kDa using HPLC-SEC coupled to refractive index (RI) detector. The MenX- Tetanus toxoid (TT) monovalent conjugate proved to be highly immunogenic in mice, and the bactericidal titers of MenX-TT conjugate were 10-fold higher than native PS. Increasing the dose of MenX-TT conjugate from 0.5 mu g to 1.0 mu g induced an 8-fold higher antibody titer as well as serum bactericidal titer. The current work suggests that the MenX-TT conjugate is a candidate vaccine against meningitis caused by Meningococcal group X strains. (C) 2013 The International Alliance for Biological Standardization. Published by Elsevier Ltd. All rights reserved.
引用
收藏
页码:160 / 168
页数:9
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