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一种分泌天然体细胞抗原超氧化物歧化酶的减毒重组鼠伤寒沙门氏菌疫苗株对小鼠李斯特菌病的保护作用。

Protection against murine listeriosis by an attenuated recombinant Salmonella typhimurium vaccine strain that secretes the naturally somatic antigen superoxide dismutase.

作者信息

Hess J, Dietrich G, Gentschev I, Miko D, Goebel W, Kaufmann S H

机构信息

Department of Immunology, University of Ulm, Germany.

出版信息

Infect Immun. 1997 Apr;65(4):1286-92. doi: 10.1128/iai.65.4.1286-1292.1997.

Abstract

A recombinant (r)-Salmonella typhimurium aroA vaccine strain was constructed which secretes the naturally somatic protein of Listeria monocytogenes, superoxide dismutase (SOD), by the HlyB/HlyD/TolC export machinery. Vaccine efficacy of the SOD-bearing carrier strain was compared with that of the p60-secreting construct, S. typhimurium p60s (J. Hess, I. Gentschev, D. Miko, M. Welzel, C. Ladel, W. Goebel, and S. H. E. Kaufmann, Proc. Natl. Acad. Sci. USA 93:1458-1463, 1996). Vaccination of mice with both constructs induced protection against a lethal challenge with the intracellular pathogen, L. monocytogenes. While the somatic listerial antigen, SOD, is immunologically uncharacterized, the naturally secreted protein of L. monocytogenes, p60, is known to be highly immunogenic. Our data emphasize the high vaccine potential of r-Salmonella constructs secreting antigens of somatic or secreted origin. Moreover, they suggest that the HlyB/HlyD/TolC-based antigen delivery system with attenuated Salmonella spp. as the carrier is capable of potentiating the immune response against foreign proteins independent from their immunogenicity in and display by the natural host.

摘要

构建了一种重组鼠伤寒沙门氏菌aroA疫苗株,该菌株通过HlyB/HlyD/TolC输出机制分泌单核细胞增生李斯特菌的天然菌体蛋白超氧化物歧化酶(SOD)。将携带SOD的载体菌株的疫苗效力与分泌p60的构建体鼠伤寒沙门氏菌p60s(J. 赫斯、I. 根切夫、D. 米科、M. 韦尔泽尔、C. 拉德尔、W. 戈贝尔和S. H. E. 考夫曼,《美国国家科学院院刊》93:1458 - 1463,1996年)的疫苗效力进行了比较。用这两种构建体对小鼠进行疫苗接种均诱导产生了针对细胞内病原体单核细胞增生李斯特菌致死性攻击的保护作用。虽然菌体李斯特菌抗原SOD的免疫学特性尚未明确,但已知单核细胞增生李斯特菌天然分泌的蛋白p60具有高度免疫原性。我们的数据强调了分泌菌体或分泌源抗原的重组沙门氏菌构建体具有很高的疫苗潜力。此外,这些数据表明,以减毒沙门氏菌属为载体、基于HlyB/HlyD/TolC的抗原递送系统能够增强针对外源蛋白的免疫反应,而与它们在天然宿主中的免疫原性和展示情况无关。

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