Molina N C, Parker C D
Department of Molecular Microbiology and Immunology, School of Medicine, University of Missouri-Columbia 65202.
Infect Immun. 1990 Aug;58(8):2523-8. doi: 10.1128/iai.58.8.2523-2528.1990.
Two plasmids which express either nearly intact or truncated filamentous hemagglutinin (FHA) from Bordetella pertussis and which are marked with a tetracycline resistance (Tcr) gene were transformed into Salmonella dublin SL1438, an aroA deletion mutant intended for use as an attenuated oral vaccine against salmonellosis. These S. dublin recombinants, when fed to mice, induced serum immunoglobulin, immunoglobulin M (IgM), and sometimes IgA antibody responses to FHA and S. dublin. In addition, IgA antibodies against FHA were found in gut wash fluids. S. dublin carrying pDB2300, a multicopy plasmid encoding truncated FHA protein, induced a better antibody response than did S. dublin carrying pDB2000, a low-copy-number plasmid encoding full-sized FHA. Administration of tetracycline to mice enhanced the stability of recombinant plasmids, and tetracycline-treated mice developed higher anti-FHA titers. Although neither strain examined is suitable for use in a human oral vaccine, these data demonstrated that an immune response against B. pertussis FHA could be induced by oral administration of live attenuated recombinant strains of S. dublin and suggested that development of a live oral attenuated vaccine against pertussis may be possible.
两种分别表达来自百日咳博德特氏菌几乎完整或截短的丝状血凝素(FHA)且带有四环素抗性(Tcr)基因标记的质粒,被转化到都柏林沙门氏菌SL1438中,该菌株是一种aroA缺失突变体,旨在用作抗沙门氏菌病的减毒口服疫苗。当将这些都柏林沙门氏菌重组体喂给小鼠时,它们诱导产生了针对FHA和都柏林沙门氏菌的血清免疫球蛋白、免疫球蛋白M(IgM),有时还有IgA抗体反应。此外,在肠道冲洗液中发现了针对FHA的IgA抗体。携带编码截短FHA蛋白的多拷贝质粒pDB2300的都柏林沙门氏菌,比携带编码全长FHA的低拷贝数质粒pDB2000的都柏林沙门氏菌诱导出更好的抗体反应。给小鼠施用四环素可增强重组质粒的稳定性,经四环素处理的小鼠产生了更高的抗FHA滴度。尽管所检测的两种菌株都不适合用于人类口服疫苗,但这些数据表明,通过口服减毒活重组都柏林沙门氏菌菌株可诱导针对百日咳博德特氏菌FHA的免疫反应,并提示开发一种抗百日咳的口服减毒活疫苗可能是可行的。