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首页> 外文会议>Conference on vaccine technology VI >A CLINICALLY VALIDATED DROSOPHILA S2 BASED VACCINE PLATFORM FOR PRODUCTION OF MALARIA VACCINES
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A CLINICALLY VALIDATED DROSOPHILA S2 BASED VACCINE PLATFORM FOR PRODUCTION OF MALARIA VACCINES

机译：用于生产疟疾疫苗的临床验证的基于果蝇S2的疫苗平台

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Drosophila S2 insect cell expression is less known than the extensively used Spodoptera or Trichoplusia ni (Hi-5) insect cell based Baculovirus expression system (BEVS). Nevertheless it has been used in research for almost 40 years. The cell line was derived from late stage Drosophila melanogaster (Fruit fly) embryos by Schneider in the 1970s, who named the cell line Drosophila Schneider line 2 (synonyms: S2, SL2, D.mel. 2). The system has been widely applied to fundamental research, where the availability of the whole genome sequence of Drosophila melanogaster (1, 2) and the S2 cells' susceptibility to RNA interference methods (3, 4) have enabled genome wide RNAi screening and whole genome expression analysis techniques to be used to great effect. S2 cells have proved to be highly effective for the production of proteins from a great variety of protein classes (5), such as: viral proteins, toxins, membrane proteins, enzyme, etc. Recent publications have also shown the strength of the S2 system in expression of Virus Like Particles (VLPs) (6). ExpreS2ion has developed the ExpreS2, Drosophila S2 platform to achieve improved yields for difficult to express proteins. Furthermore, several technologies have been developed to improve the ease of use of the system, as well as enable fast and efficient screening of multiple constructs. S2 based production processes for two malaria vaccine clinical trails with The Jenner Institute, Oxford University (Rh5 (7,8), blood-stage malaria) and Copenhagen University (VAR2CSA (9) pregnancy associated malaria) have been developed. The placental malaria vaccine is currently in a phase la trail in Germany, and a Phase lb trial in Benin. The blood-stage malaria vaccine is currently in Phase Ma trial and is expecting results by the end of 2018. Several transmission-blocking candidates have been identified over the years with some of the most prominent being pfs48/45, Pfs230C and Pfs25(10). Other vaccine targets focus on blood-stage malaria such as Rh5, PfRIPR and CyrPA. We will present data on the development of a high producing Pfs25 monoclonal cell line and the purification from said cell line,as well as expression data on a range of other malaria vaccine targets. This present the clinically validated ExpreS2 platform as a complete system for a wide range of malaria targeting vaccines.
机译：果蝇S2昆虫细胞的表达远不如广泛使用的斜纹夜蛾或Trichoplusia ni（Hi-5）基于昆虫细胞的杆状病毒表达系统（BEVS）。尽管如此，它已经在研究中使用了近40年。该细胞系源自1970年代Schneider的后期果蝇胚胎（果蝇）胚胎，后者将其命名为果蝇Schneider系2（同义词：S2，SL2，D.mel。2）。该系统已广泛应用于基础研究，其中果蝇的整个基因组序列的可用性（1、2）和S2细胞对RNA干扰方法的敏感性（3、4）使得能够进行全基因组的RNAi筛选和整个基因组表达分析技术将获得巨大效果。事实证明，S2细胞可高效生产多种蛋白质类型的蛋白质（5），例如：病毒蛋白质，毒素，膜蛋白，酶等。最近的出版物也显示了S2系统的强度病毒样颗粒（VLP）的表达（6）。 ExpreS2ion开发了果蝇S2平台ExpreS2，以提高难以表达的蛋白质的产量。此外，已经开发了几种技术来改善系统的易用性，并能够快速有效地筛选多种构建体。已经开发了牛津大学詹纳研究所（Rh5（7,8），血液阶段疟疾）和哥本哈根大学（VAR2CSA（9）妊娠相关疟疾）的两种疟疾疫苗临床试验的基于S2的生产工艺。胎盘疟疾疫苗目前在德国处于la阶段，在贝宁处于lb阶段。血液阶段疟疾疫苗目前处于Ma期试验中，预计将于2018年底获得结果。多年来，已经确定了几种阻止传播的候选药物，其中最著名的是pf​​s48 / 45，Pfs230C和Pfs25（10）。 。其他疫苗目标针对血液阶段的疟疾，例如Rh5，PfRIPR和CyrPA。我们将提供有关高产Pfs25单克隆细胞系开发和从所述细胞系纯化的数据，以及一系列其他疟疾疫苗靶标的表达数据。这代表了经过临床验证的ExpreS2平台，可作为针对多种疟疾靶向疫苗的完整系统。

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