Study of a tick-borne encephalitis vaccine

O. V. Stronin, A. A.  Epanchintsev, A.  A. Koltunov
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Abstract

Scientific relevance. Tick-borne encephalitis is one of the most significant anthropozoonoses   for public health in the Russian Federation. Wide vaccination coverage is required to control  this zoonotic infection. However, large-scale immunisation is not feasible without developing novel vaccines with improved safety and efficacy profiles, such as vaccines based on the continuous Vero cell line.Aim. This extended study aimed to investigate the key quality attributes of VeroKSEN, a new tick-borne encephalitis vaccine that was obtained using Vero cells.Materials and methods. The authors implemented current approaches to vaccine development, including propagation of tick-borne encephalitis strain 205 (Far Eastern subtype) in Vero cells, fine purification of the viral antigen by size-exclusion chromatography on polymeric resins, and introduction of additional quality control methods. For VeroKSEN production, the authors used the method protected by utility patent No. 2678431.  Quality control of the finished product  was performed according to the State Pharmacopoeia of the Russian Federation. The laboratory study of the vaccine and its intermediates in Balb/с mice used novel control methods developed by the authors. Additional methods included polyacrylamide gel electrophoresis, enzyme immunoassay, immunoblotting with total antibodies to tick-borne encephalitis virus  and monoclonal antibodies to glycoprotein E, reverse transcription–polymerase chain reaction, and high-performance liquid chromatography. The extended potency study used test strains of different subtypes, including Absettarov (Western), Sofjin (Far Eastern), and Korzukhin (Siberian). The authors studied the infectious activity of tick-borne encephalitis virus in outbred mice using the pharmacopoeial titration method. Statistical analysis of the study results involved calculating the arithmetic mean and the root-mean-square deviation.Results. The authors studied the key quality attributes of VeroKSEN and its intermediates. Selected inactivation conditions reduced the infectious activity of the viral harvest to an undetectable level within 24 h, while its antigenic activity remained approximately 100% of the baseline. The fine purification stages and the methods and techniques developed by the authors provided a whole-virion fraction with a purity of up to 98.2% and removed process-related impurities (residual host-cell DNA, bovine serum albumin, formaldehyde, and bacterial endotoxins) to the levels required by national legislation. The stability study demonstrated    that the vaccine met the requirements for up to 36 months.Conclusions. The study showed the high potency of the new vaccine in terms of protection against the Western, Siberian, and Far Eastern subtypes of tick-borne encephalitis, with minimum immunising doses (MID50) of 0.007, 0.00125, and 0.00093 mL, respectively.
蜱传脑炎疫苗的研究
科学相关性。蜱传脑炎是俄罗斯联邦公共卫生最重要的人畜共患病之一。为控制这种人畜共患感染,需要广泛接种疫苗。然而,如果不开发出安全性和有效性更高的新型疫苗,例如基于连续Vero细胞系的疫苗,大规模免疫是不可行的。的目标。这项扩展研究旨在调查VeroKSEN的关键质量属性,VeroKSEN是一种使用Vero细胞获得的新型蜱传脑炎疫苗。材料和方法。作者实施了目前的疫苗开发方法,包括在Vero细胞中繁殖蜱传脑炎菌株205(远东亚型),通过聚合物树脂的大小隔离层析对病毒抗原进行精细纯化,以及引入额外的质量控制方法。对于VeroKSEN的生产,作者使用了受实用专利号2678431保护的方法。成品的质量控制按照俄罗斯联邦国家药典进行。该疫苗及其中间体在Balb/ r小鼠中的实验室研究使用了作者开发的新控制方法。其他方法包括聚丙烯酰胺凝胶电泳、酶免疫测定、蜱传脑炎病毒总抗体和糖蛋白E单克隆抗体免疫印迹、逆转录-聚合酶链反应和高效液相色谱法。扩展效力研究使用了不同亚型的试验菌株,包括Absettarov(西部),Sofjin(远东)和Korzukhin(西伯利亚)。采用药检滴定法研究了蜱传脑炎病毒在远交种小鼠体内的传染活性。研究结果的统计分析包括计算算术平均值和均方根偏差。结果。作者研究了VeroKSEN及其中间体的关键质量属性。选定的失活条件将病毒收获的感染活性降低到24小时内检测不到的水平,而其抗原活性保持在基线的100%左右。作者开发的精细纯化阶段和方法和技术提供了纯度高达98.2%的全病毒粒子部分,并将过程相关的杂质(残余宿主细胞DNA、牛血清白蛋白、甲醛和细菌内毒素)去除到国家立法要求的水平。稳定性研究表明,该疫苗符合长达36个月的要求。结论。该研究表明,新疫苗在预防西部、西伯利亚和远东蜱传脑炎亚型方面具有很高的效力,最低免疫剂量(MID 50)分别为0.007、0.00125和0.00093 mL。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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