Secretory delivery of recombinant proteins in attenuated Salmonella strains:: potential and limitations of Type I protein transporters
Secretory delivery of recombinant proteins in attenuated Salmonella strains:: potential and limitations of Type I protein transporters
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DOI：
10.1016/s0928-8244(03)00092-0
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发表时间：
2003-07-15
影响因子：
--
通讯作者：
von Specht, BU
中科院分区：
文献类型：
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作者：
Hahn, HP;von Specht, BU
减毒活沙门氏菌菌株已被广泛探索作为具有免疫佐剂和免疫调节潜力的重组疫苗抗原和效应蛋白的口服递送系统。这种方法的可行性在各种抗原的人体疫苗接种试验中得到了证明。然而，与使用相同疫苗抗原的肠胃外免疫中监测到的免疫效率相比，活疫苗的免疫效率通常显着较低。这至少部分是由于缺乏分泌表达系统，使得这些菌株能够大规模地向细胞外递送疫苗和效应蛋白。由于 I 型（ATP 结合盒）分泌系统复杂性低且分泌信号位于分泌蛋白的末端，因此似乎特别适合开发此类重组细胞外表达系统。迄今为止，大肠杆菌溶血素系统是唯一已适应沙门氏菌重组蛋白分泌的I型分泌系统。然而，该系统存在许多缺点，包括分泌能力低、遗传调控复杂以及对分泌蛋白的结构限制，最终阻碍了重组疫苗和效应蛋白的高水平体内递送。因此，基于 I 型输出蛋白开发更有效的重组蛋白分泌系统有助于提高重组沙门氏菌活疫苗的功效。 I 型分泌系统介导细菌表面层蛋白的分泌，例如新月柄杆菌中的 RsaA，被认为是改进分泌递送系统的有希望的候选者。 (C) 2003 年欧洲微生物学会联合会。由 Elsevier Science B.V. 出版。保留所有权利。
Live attenuated Salmonella strains have been extensively explored as oral delivery systems for recombinant vaccine antigens and effector proteins with immunoadjuvant and immunomodulatory potential. The feasibility of this approach was demonstrated in human vaccination trials for various antigens. However, immunization efficiencies with live vaccines are generally significantly lower compared to those monitored in parenteral immunizations with the same vaccine antigen. This is, at least partly, due to the lack of secretory expression systems, enabling large-scale extracellular delivery of vaccine and effector proteins by these strains. Because of their low complexity and the terminal location of the secretion signal in the secreted protein, Type I (ATP-binding cassette) secretion systems appear to be particularly suited for development of such recombinant extracellular expression systems. So far, the Escherichia coli hemolysin system is the only Type I secretion system, which has been adapted to recombinant protein secretion in Salmonella. However, this system has a number of disadvantages, including low secretion capacity, complex genetic regulation, and structural restriction to the secreted protein, which eventually hinder high-level in vivo delivery of recombinant vaccines and effector proteins. Thus, the development of more efficient recombinant protein secretion systems, based on Type I exporters can help to improve efficacies of live recombinant Salmonella vaccines. Type I secretion systems, mediating secretion of bacterial surface layer proteins, such as RsaA in Caulobacter crescentus, are discussed as promising candidates for improved secretory delivery systems. (C) 2003 Federation of European Microbiological Societies. Published by Elsevier Science B.V. All rights reserved.