口服重组B亚单位O1/O139霍乱疫苗的制备及检定
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摘要
目的制备口服重组B亚单位O1/O139霍乱疫苗,并进行全面检定。方法制备O1、O139群霍乱弧菌灭活菌体原液及重组霍乱毒素B亚单位(recombinant cholera toxin B subunit,r CTB)原液,按比例混合制成口服重组B亚单位O1/O139霍乱疫苗,为保护r CTB免受胃酸的破坏,制备了碳酸氢钠抗酸泡腾颗粒,并按照制定的新制品原液及成品的质控标准,对原液及成品进行全面检定。结果制备的口服重组B亚单位O1/O139霍乱疫苗工艺稳定,各项指标均达到质控标准。结论口服重组B亚单位O1/O139霍乱疫苗安全、有效,且制备工艺可行,符合规模化生产的要求。
Objective To prepare oral bivalent recombinant cholera toxin B subunit-O1 / O139 whole cell cholera vaccine and perform overall control tests. Methods Bulks of inactivated Vibrio cholera groups O1 and O139 as well as the bulk of recombinant cholera toxin B subunit(r CTB) were prepared and mixed at the specified proportion to obtain oral r CTBO1 / O139 whole cell cholrea vaccine. The vaccine was prepared into acid-resistant sodium bicarbonate effervescent particles to prevent r CTB from damage by gastric acid, and subjected to overall control tests according to the standard for qual-ity control of bulk and final product of novel preparations. Results The procedure for preparation of oral bivalent r CTBO1 / O139 whole cell cholera vaccine was stable, and all the quality indexes of prepared vaccine met the standard for quality control. Conclusion The oral bivalent r CTB-O1 / O139 whole cell cholera vaccine was safe and effective, of which the preparation procedure was feasible and met the requirements for large-scale production.
Objective To prepare oral bivalent recombinant cholera toxin B subunit-O1 / O139 whole cell cholera vaccine and perform overall control tests. Methods Bulks of inactivated Vibrio cholera groups O1 and O139 as well as the bulk of recombinant cholera toxin B subunit(r CTB) were prepared and mixed at the specified proportion to obtain oral r CTBO1 / O139 whole cell cholrea vaccine. The vaccine was prepared into acid-resistant sodium bicarbonate effervescent particles to prevent r CTB from damage by gastric acid, and subjected to overall control tests according to the standard for qual-ity control of bulk and final product of novel preparations. Results The procedure for preparation of oral bivalent r CTBO1 / O139 whole cell cholera vaccine was stable, and all the quality indexes of prepared vaccine met the standard for quality control. Conclusion The oral bivalent r CTB-O1 / O139 whole cell cholera vaccine was safe and effective, of which the preparation procedure was feasible and met the requirements for large-scale production.
引文
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[15]QUIDING M,NORDSTRM I,KILANDER A,et al.Intestinal immune responses in humans.Oral cholera vaccination induces strong intestinal antibody responses and interferon-gamma production and evokes local immunological memory[J].J Clin Invest,1991,88(1):143-148.
[2]LI B S,TAN H L,WANG D C,et al.Etiologic characteristics of Vibrio cholerae in Guangdong province in 2009-2013[J].Chin J Epidemiol,2014,35(7):825-831.(in Chinese)李柏生,谭海玲,王多春,等.广东省2009-2013年霍乱弧菌病原学特征分析[J].中华流行病学杂志,2014,35(7):825-831.
[3]ZHAO X,ZHANG L,LI J,et al.Phenotypic diversity of toxigenic Vibrio cholerae O1 El Tor strains identified in China[J].Chin J Epidemiol,2014,35(5):573-575.(in Chinese)赵璇,张力,李杰,等.中国O1群El Tor霍乱弧菌产毒株表型多态性研究[J].中华流行病学杂志,2014,35(5):573-575.
[4]TU L H,CHEN M,LI W,et al.Characterization of phenotype and molecular characteristics on Vibrio cholerae strains isolated[J].Chin J Epidemiol,2013,34(8):815-818.(in Chinese)屠丽红,陈敏,李伟,等.上海市1962-2011年霍乱弧菌表型特征及分子分型研究[J].中华流行病学杂志,2013,34(8):815-818.
[5]YAN H,SHI L,CAO Y C,et al.Distribution of drugresistance related integrons of Vibrio cholerae isolated between1993 and 2000[J].Chin J Infect Dis,2007,25(8):454-457.(in Chinese)闫鹤,石磊,曹以诚,等.1993-2000年霍乱弧菌耐药整合子的分布状况[J].中华传染病杂志,2007,25(8):454-457.
[6]DESAI S N,AKALU Z,TESHOME S,et al.A randomized,placebo-controlled trial evaluating safety and immunogenicity of the killed,bivalent,whole-cell oral cholera vaccine in Ethiopia[J].Am J Trop Med Hyg,2015,93(3):527-533.
[7]QADRI F,ALI M,CHOWDHURY F,et al.Feasibility and effectiveness of oral cholera vaccine in an urban endemic setting in Bangladesh:a cluster randomised open-label trial[J].Lancet,2015,386(10001):1362-1371.
[8]魏承毓.O139霍乱简介[J].中级医刊,1995,30(7):4-6.
[9]SAHA A,CHOWDHURY M I,KHANAM F,et al.Safety and immunogenicity study of a killed bivalent(O1 and O139)whole-cell oral cholera vaccine Shanchol,in Bangladeshi adults and children as young as 1 year of age[J].Vaccine,2011,29(46):8285-8292.
[10]Chinese Pharmacopoeia Commission.Pharmacopoeia of People's Republic of China(VolⅡ)[S].Beijing:China Med Sci Press,2010:Appendix 14-15.(in Chinese)中华人民共和国药典委员会.中华人民共和国药典(二部)[S].北京:中国医药科技出版社,2010:附录14-15.
[11]Chinese Pharmacopoeia Commission.Pharmacopoeia of People's Republic of China(VolⅢ)[S].Beijing:China Med Sci Press,2010:Appendix 54-109.(in Chinese)中华人民共和国药典委员会.中华人民共和国药典(三部)[S].北京:中国医药科技出版社,2010:附录54-109.
[12]European Pharmacopoeia Commission.European Pharmacopoeia7.0[S].Strasbourg:European Directorate for the Quality Control of Medicines,2011:748-751.
[13]World Health Organization.Guidelines for the production and control of inactivated oral cholera vaccines[J].WHO TRS,2004,924:1-232.
[14]NAG S,DAS S,CHAUDHURI K.In vivo induced clp B1 gene of Vibrio cholerae is involved in different stress responses and affects in vivo cholera toxin production[J].Biochem Biophys Res Commun,2005,331(4):1365-1373.
[15]QUIDING M,NORDSTRM I,KILANDER A,et al.Intestinal immune responses in humans.Oral cholera vaccination induces strong intestinal antibody responses and interferon-gamma production and evokes local immunological memory[J].J Clin Invest,1991,88(1):143-148.