Process development for the production of an E. coli produced clinical grade recombinant malaria vaccine for Plasmodium vivax

Process development for the production of an E. coli produced clinical grade recombinant malaria vaccine for Plasmodium vivax
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DOI:
10.1016/j.vaccine.2008.12.027
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发表时间:
2009-02-25
期刊:
影响因子:
5.5
通讯作者:
Yadava, Anjali
Yadava, Anjali
中科院分区:
医学3区
文献类型:
--
作者:
Bell, Brian A.;Wood, James F.;Yadava, Anjali

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全球根除疟疾将需要开发疫苗,以防止疟原虫在恶性疟原虫之外受到疟原虫的感染。为了促进这一努力,我们先前已经报道了基于p vivax的pur虫蛋白蛋白的疫苗的克隆和表达。合成疫苗编码的全长分子涵盖了N末端和C末端区域的嵌入式嵌合重复区域,该区域代表VK210和VK247,这是VK210和VK247,这是VIVAX CSP的两个主要等位基因。使用三柱纯化方案将疫苗指定为Vivax疟疾蛋白001(VMP001),纯化至> 95%的均匀性,并具有较低的内毒素水平,并通过了Rabbit Pyrenogentionsessay。该蛋白质通过针对两个重复基序的单克隆抗体以及多克隆抗体识别。使用Montanide ISA 720使用VMP001免疫在小鼠中诱导的高滴度抗体。目前,我们有10,000多剂的纯化散装和1800瓶配方的散装疫苗可用于临床测试,而VMP001目前正在接受进一步的发育,以预防进一步的发育,以预防候选疫苗。人类。由Elsevier Ltd.出版。
The global eradication of malaria will require the development of vaccines to prevent infection cause by Plasmodium vivax in addition to Plasmodium falciparum. In an attempt to contribute to this effort we have previously reported the cloning and expression of a vaccine based on the circumsporozoite protein of P vivax. The synthetic vaccine encodes for a full-length molecule encompassing the N-terminal and C-terminal regions flanking a chimeric repeat region representing VK210 and VK247, the two major alleles of P. vivax CSP. The vaccine, designated vivax malaria protein 001 (VMP001), was purified to >95% homogeneity using a three-column purification scheme and had low endotoxin levels and passed the rabbit pyrogenicity assay. The protein is recognized by monoclonal antibodies directed against the two repeat motifs, as well as polyclonal antibodies. Immunization with VMP001 induced high titer antibodies in mice using Montanide ISA 720. We currently have More than 10,000 doses of purified bulk and 1800 vials of formulated bulk vaccine available for clinical testing and VMP001 is currently undergoing further development as a candidate vaccine to prevent malaria in humans. Published by Elsevier Ltd.