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    • 6. 发明授权
    • Recombinant bacterial vaccine system with environmentally limited viability
    • 具有环境有限生命力的重组细菌疫苗系统
    • US07871604B1
    • 2011-01-18
    • US09120970
    • 1998-07-22
    • Roy Curtiss, IIISteven A. Tinge
    • Roy Curtiss, IIISteven A. Tinge
    • C12N1/21A01N63/00
    • C12N15/64C12N15/70C12N15/74
    • Disclosed is an Environmentally Limited Viability System (ELVS) for microorganisms based on temperature differences between permissive and non-permissive environments. Viability of the microorganisms are limited to the permissive environment by specifically expressing one or more essential genes only in the permissive environment, or expressing one or more lethal genes only in the non-permissive environment. Environmentally Limited Viability Systems are also disclosed involving coordinate expression of a combination of required genes and lethal genes. Microorganisms containing an Environmentally Limited Viability System are useful for release into a permissive environment. Temperature regulated Environmentally Limited Viability Systems are particularly suited for use with recombinant avirulent Salmonella vaccines by limiting their growth to the warmer environment inside the host. Such vaccines can be administered to protect humans or warm-blooded animals against bacterial, viral, mycotic and parasitic pathogens, especially those that colonize on or invade through mucosal surfaces. This antigen delivery system can also be used for expression of gamete-specific antigens to induce immune responses to block fertilization, or to induce immune responses to tumor antigens. In the event that an individual sheds live vaccine into the environment, the presence of the ELVS prevents survival of the vaccine. When environmentally regulated lethal genes are present on an extrachromosomal element and are regulated by chromosomal genes, transfer of the extrachromosomal element to other microorganisms will be limited by unregulated expression of the lethal genes in the recipient microorganism.
    • 公开了基于许可和非允许环境之间的温度差异的微生物的环境有限的生存力系统(ELVS)。 通过仅在许可环境中特异性表达一个或多个必需基因,或仅在非允许环境中表达一个或多个致死基因,微生物的活力受到许可环境的限制。 还公开了环境有限的可行性系统,涉及协调所需基因和致死基因组合的表达。 含有环境有限的生命力系统的微生物对于释放到允许的环境中是有用的。 温度调节环境有限的生命力系统特别适用于重组无毒性沙门氏菌疫苗,通过将其生长限制在主机内较暖的环境中。 可以施用这样的疫苗以保护人类或温血动物免受细菌,病毒,真菌和寄生虫病原体,特别是通过粘膜表面侵袭或入侵的病原体。 该抗原递送系统还可用于表达配子特异性抗原以诱导阻断受精的免疫应答,或诱导对肿瘤抗原的免疫应答。 如果一个人将活疫苗流入环境,则ELVS的存在可防止疫苗的存活。 当环境调节的致死基因存在于染色体外元件上并且被染色体基因调节时,染色体外元件转移到其他微生物将受到受体微生物中致死基因的不受调节的表达的限制。