Chatfield S, Roberts M, Londono P, Cropley I, Douce G, Dougan G
Department of Biochemistry, Imperial College of Science, Technology and Medicine, London, UK.
FEMS Immunol Med Microbiol. 1993 Jun;7(1):1-7. doi: 10.1111/j.1574-695X.1993.tb00374.x.
Safe, live attenuated Salmonella strains can be produced by introducing defined non-reverting mutations into the chromosome. Such rationally attenuated strains have proved to be excellent oral vaccines in several animal species and can therefore be considered as candidate vaccines against invasive salmonellosis in both animals and man. A panel of attenuating lesions is now available from which it is possible to tailor the level of attenuation and hence produce strains with different immunogenic properties. Because of the spectrum of immune responses produced by such Salmonella vaccine strains they have been utilised extensively as vectors for delivering heterologous antigens to the mammalian immune system. We have focussed on the development of a single dose oral tetanus vaccine based on attenuated Salmonella strains expressing a non-toxic, immunogenic protein derived from tetanus toxin (fragment C). Several different expression systems have been used for fragment C and candidate vaccine strains have been constructed that are capable of protecting orally immunised mice against a lethal challenge with tetanus toxin. An oral tetanus vaccine may help to reduce the mortality rate from tetanus in the developing world by overcoming the problems associated with the implementation of vaccine programmes using the current parenteral vaccine.
通过将特定的非回复突变引入染色体，可以制备安全的减毒活沙门氏菌菌株。这种经过合理减毒的菌株已被证明是几种动物物种中出色的口服疫苗，因此可被视为预防动物和人类侵袭性沙门氏菌病的候选疫苗。现在有一组减毒损伤可供选择，利用这些损伤可以调整减毒水平，从而生产出具有不同免疫原性的菌株。由于此类沙门氏菌疫苗菌株产生的免疫反应谱，它们已被广泛用作将异源抗原递送至哺乳动物免疫系统的载体。我们专注于开发一种基于表达源自破伤风毒素（片段C）的无毒免疫原性蛋白的减毒沙门氏菌菌株的单剂量口服破伤风疫苗。已使用几种不同的表达系统来表达片段C，并构建了候选疫苗菌株，这些菌株能够保护经口服免疫的小鼠免受破伤风毒素的致死性攻击。口服破伤风疫苗通过克服使用当前注射用疫苗实施疫苗计划所带来的问题，可能有助于降低发展中国家破伤风的死亡率。
