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Comparison of a fimbrial versus an autotransporter display system for viral epitopes on an attenuated Salmonella vaccine vector

机译:减毒沙门氏菌疫苗载体上病毒抗原决定簇的纤维与自动转运展示系统的比较

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摘要

Attenuated Salmonella have been used as vectors to deliver foreign antigens as live vaccines. We have previously developed an efficient surface-display system by genetically engineering 987P fimbriae to present transmissible gastroenteritis virus (TGEV) C and A epitopes for the induction of anti-TGEV antibodies with a Salmonella vaccine vector. Here, this system was compared with an autotransporter protein surface display system. The TGEV C and A epitopes were fused to the passenger domain of the MisL autotransporter of Salmonella. Expression of both the MisL- and 987P subunit FasA-fusions to the TGEV epitopes were under the control of in vivo-induced promoters. Expression of the TGEV epitopes from the Salmonella typhimurium CS4552 (crp cya asd pgtE) vaccine strain was greater when the epitopes were fused to MisL than when they were fused to the 987P FasA subunit. However, when BALB/c mice were orally immunized with the Salmonella vector expressing the TGEV epitopes from either one of the fusion constructs or both together, the highest level of anti-TGEV antibody was obtained with the 987P-TGEV immunogen-displaying vector. This result suggested that better immune responses towards specific epitopes could be obtained by using a polymeric display system such as fimbriae.
机译:减毒沙门氏菌已被用作载体,以活疫苗的形式输送外来抗原。我们以前已经通过对987P菌毛进行基因工程开发了一种有效的表面展示系统,以展示可传播的胃肠炎病毒(TGEV)C和A抗原决定簇,以利用沙门氏菌疫苗载体诱导抗TGEV抗体。在此,将该系统与自转运蛋白表面展示系统进行了比较。 TGEV C和A表位融合到沙门氏菌的MisL自转运蛋白的乘客域。 MisL和987P亚基FasA融合体在TGEV表位上的表达均在体内诱导的启动子的控制下。当将表位融合到MisL时,来自鼠伤寒沙门氏菌CS4552(crp cya asd pgtE)疫苗株的TGEV表位的表达要比将它们融合到987P FasA亚基时的表达高。然而,当用表达来自融合构建体之一或两者的TGEV表位的沙门氏菌载体口服免疫BALB / c小鼠时,用987P-TGEV免疫原展示载体获得了最高水平的抗TGEV抗体。该结果表明,通过使用聚合物展示系统例如菌毛,可以获得对特定表位的更好的免疫应答。

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