O'Callaghan D, Maskell D, Tite J, Dougan G
Department of Molecular Biology, Wellcome Biotech, Beckenham, Kent, U.K.
Immunology. 1990 Feb;69(2):184-9.
Two near isogenic strains of Salmonella typhimurium HWSH, stably mutated in either the aroA gene affecting the biosynthesis of aromatic compounds, or the purA gene affecting the biosynthesis of purines, were administered intravenously as live attenuated vaccines to BALB/c mice. HWSH aroA-immunized mice were well protected against intravenous (i.v.) challenge with wild-type virulent HWSH for at least 10 weeks, whereas HWSH purA-immunized mice were unprotected. Furthermore, HWSH aroA-immunized mice could also control a heterologous challenge with virulent Listeria monocytogenes at 7 and 14 days post-immunization, whereas mice receiving a similar dose of HWSH purA could not. Increasing the i.v. dose of HWSH purA compared to HWSH aroA induced some resistance to L. monocytogenes. Induction of early anti-S. typhimurium resistance by HWSH aroA immunization appeared slightly later than the anti-L. monocytogenes resistance. Mice immunized with either vaccine were able to mount S. typhimurium-specific T-cell proliferative responses and produced anti-S. typhimurium humoral antibodies in their serum. The antibody titre was greater in those mice immunized with the aroA mutant.
将两株鼠伤寒沙门氏菌HWSH的近等基因株静脉注射给BALB/c小鼠,作为减毒活疫苗。这两株菌分别在影响芳香族化合物生物合成的aroA基因或影响嘌呤生物合成的purA基因中发生了稳定突变。用aroA基因缺失的HWSH免疫的小鼠,对野生型强毒HWSH的静脉攻击具有良好的保护作用,至少持续10周,而用purA基因缺失的HWSH免疫的小鼠则没有受到保护。此外,用aroA基因缺失的HWSH免疫的小鼠在免疫后7天和14天也能抵御强毒单核细胞增生李斯特菌的异源攻击,而接受相同剂量purA基因缺失的HWSH的小鼠则不能。与aroA基因缺失的HWSH相比,增加purA基因缺失的HWSH的静脉注射剂量可诱导对单核细胞增生李斯特菌的一些抗性。aroA基因缺失的HWSH免疫诱导的早期抗鼠伤寒沙门氏菌抗性出现的时间略晚于抗单核细胞增生李斯特菌抗性。用任何一种疫苗免疫的小鼠都能够产生鼠伤寒沙门氏菌特异性T细胞增殖反应,并在血清中产生抗鼠伤寒沙门氏菌的体液抗体。用aroA突变体免疫的小鼠的抗体滴度更高。