Structural conformers produced during malaria vaccine production in yeast
Structural conformers produced during malaria vaccine production in yeast
复制标题
酵母生产疟疾疫苗过程中产生的结构构象异构体
作者：
A. Stowers;Yanling Zhang;R. Shimp;D. Kaslow
基于酿酒酵母的重组蛋白表达系统已用于表达疟疾疫苗候选抗原。如此产生的抗原已用于三个一期临床试验和许多临床前非人类灵长类动物试验。计划使用这些候选疫苗抗原进行进一步的一期试验。这些分子被认为是抗疟疫苗的有吸引力的候选分子，因为它们在寄生虫生命周期的某个阶段都暴露在表面。它们都有一个不寻常的结构特征：表皮生长因子（EGF）样基序。当这些蛋白质在我们的酿酒酵母表达系统中表达时，它们会产生一系列稳定的结构构象异构体，每种构象异构体都具有不同的二硫键模式。这导致了构象异构体之间的生物化学差异，更重要的是抗原差异（例如抗体 B 细胞表位的存在或不存在）。这些发现对于酿酒酵母中表达的其他含有 EGF 结构域的蛋白质或含有该生物体通常不表达的其他半胱氨酸折叠基序的蛋白质具有重要影响，无论是用于疫苗生产还是用于研究/试剂目的。版权所有 © 2000 约翰·威利父子有限公司
A recombinant protein expression system based on Saccharomyces cerevisiae has been used to express malarial vaccine candidate antigens. The antigens so produced have been used in three Phase 1 clinical trials and numerous preclinical non‐human primate trials. Further Phase I trials are planned using these candidate vaccine antigens. These molecules were identified as attractive candidates for antimalarial vaccines, as they are all surface‐exposed at some stage in the parasite's life cycle. They all share an unusual structural feature: epidermal growth factor (EGF)‐like motifs. When these proteins are expressed in our S. cerevisiae expression system, they are produced as a series of stable structural conformers, each with a different disulphide bonding pattern. This leads to both biochemical and, more importantly, antigenic differences between the conformers (e.g. presence or absence of an antibody B cell epitope). These findings have important ramifications for other EGF‐domain‐containing proteins expressed in S. cerevisiae, or for proteins which contain other cysteine‐folding motifs not normally expressed by this organism, both for vaccine production or for research/reagent purposes. Copyright © 2000 John Wiley & Sons, Ltd.
影响因子：
1.5
作者：
KASLOW, DC;HUI, G;KUMAR, S
通讯作者：
KUMAR, S