公开(公告)号：US08183026B2

公开(公告)日：2012-05-22

申请号：US10541246

申请日：2004-01-14

申请人： Mark L. Lawrence ,  Daniel B. Paulsen ,  Daniel W. Scruggs

发明人： Mark L. Lawrence ,  Daniel B. Paulsen ,  Daniel W. Scruggs

IPC分类号： A01N63/00 ,  C12N1/00 ,  C12N1/12 ,  C12N1/36

CPC分类号： C12N9/1007 ,  A61K2039/522 ,  Y02A50/484

摘要： Live attenuated bacteria vaccines are provided. Also provided are methods by which such vaccines can be obtained, including: a method by which a copy of the dam gene from a pathogenic bacteria is cloned into a plasmid capable of replication in the same bacteria species such that it is overexpressed from either a lac promoter, tac promoter, araBAD promoter, trc promoter, trp promoter, T7, SP6, or T5 bacteriophage promoters, a native promoter from that species, or other appropriate promoter. The plasmid containing the dam gene is then transferred into the pathogens to cause increased expression of Dam resulting in the formation of a live attenuated bacterial vaccines. Alternative methods for producing the vaccine are also provided including altering or replacing the chromosomal promoter for the native dam gene so as to alter Dam expression or mutating or replacing the native dam gene so as to alter the expression of Dam in a pathogenic bacteria.

摘要翻译： 提供活的减毒细菌疫苗。 还提供了可以获得这样的疫苗的方法，包括：将来自病原菌的dam基因的拷贝克隆到能够在相同细菌种中复制的质粒的方法，使得其从lac 启动子，tac启动子，araBAD启动子，trc启动子，trp启动子，T7，SP6或T5噬菌体启动子，来自该物种的天然启动子或其他合适的启动子。 然后将含有该基因的质粒转移到病原体中以导致Dam的表达增加，导致减毒细菌疫苗的形成。 还提供了用于生产疫苗的替代方法，包括改变或替代天然阻断基因的染色体启动子，以便改变大坝表达或突变或替代天然阻断基因，从而改变病原菌中的表达。