Production of a conjugate vaccine for Salmonella enterica serovar Typhi from Citrobacter Vi
Production of a conjugate vaccine for Salmonella enterica serovar Typhi from Citrobacter Vi
复制标题
DOI：
10.1016/j.vaccine.2011.11.108
复制
发表时间：
2012-01-20
期刊：
影响因子：
5.5
通讯作者：
Martin, L. B.
中科院分区：
文献类型：
--
作者：
Micoli, F.;Rondini, S.;Martin, L. B.
通过使用N-（3-二甲基氨基丙基）-N '-乙基碳二亚胺偶联化学，经由己二酸二酰肼间隔基将从柠檬酸杆菌纯化的Vi与无毒突变白喉毒素CRM 197化学连接，产生用于伤寒沙门氏菌血清型的缀合物疫苗。基于用十六烷基三甲基溴化铵（CTAB）从培养上清液中沉淀Vi，用乙醇溶解CTA-多糖盐，然后用Na+交换CTA（+）抗衡离子，开发了多糖纯化过程。纯化的Vi多糖完全O-乙酰化，纯度高。对结合工艺进行了优化，以获得可扩展的工艺，该工艺已用于目前临床试验中疫苗的中试规模GMP生产。(C)2011爱思唯尔有限公司版权所有。
A conjugate vaccine for Salmonella enterica serovar Typhi was produced by chemically linking Vi, purified from Citrobacter, to the non-toxic mutant diphtheria toxin CRM197 via an adipic dihydrazide spacer using N-(3-Dimethylaminopropy1)-N'-ethylcarbodiimide coupling chemistry. The polysaccharide purification process was developed based on Vi precipitation from culture supernatant with cetyl trimethylammonium bromide (CTAB), solubilization of the CTA-polysaccharide salt with ethanol followed by exchange of the CTA(+) counter ion with Na+. The purified Vi polysaccharide was fully O-acetylated and with high purity. The conjugation process was optimized to obtain a scalable process that has been used for GMP production at pilot scale of vaccine currently in clinical trials. (C) 2011 Elsevier Ltd. All rights reserved.