02-01-2020 дата публикации
Номер: US20200002408A1
Принадлежит:
The present invention provides novel, recombinant Gram-negative bacteria. In particular, the invention provides recombinant Gram-negative bacteria (e.g., ) lacking genes involved in lipopolysaccharide (LPS, endotoxin) biosynthesis (e.g., lacking genes required for core oligosaccharide biosynthesis) and also provides recombinant Gram-negative bacteria lacking genes involved in LPS biosynthesis that contain one or more exogenous KDO transferases and/or one or more exogenous heptosyltransferases (e.g., from one or more types and/or strains of bacteria). The invention further provides methods of generating and utilizing (e.g., as or in an immunogenic composition (e.g., as or in an adjuvant and/or vaccine)) the recombinant Gram-negative bacteria therapeutic, preventative, and/or research applications. 1. A recombinant Gram-negative bacterial cell lacking all endogenous glycosyltransferases involved in core oligosaccharide biosynthesis within lipopolysaccharide (LPS).2. The recombinant Gram-negative bacterial cell of claim 1 , wherein the cell lacks endogenous waaF claim 1 , waaC claim 1 , waaL claim 1 , waaU claim 1 , waaZ claim 1 , waaY claim 1 , waaJ claim 1 , waaR claim 1 , waaB claim 1 , waaS claim 1 , waaP claim 1 , waaG claim 1 , waaQ claim 1 , and waaA genes.3. The recombinant Gram-negative bacterial cell of claim 1 , wherein the cell possesses endogenous hldD and coaD genes.4. The recombinant Gram-negative bacterial cell of claim 1 , wherein the cell generates sugar precursors of core oligonucleotide biosynthesis but lacks the capability to transfer these sugars to the Lipid IVmolecule.5Escherichia, Shigella., Salmonella, Campylobacter, Neisseria, Haemophilus, Aeromonas, Francisella, Yersinia, Klebsiella, Bordetella, Legionella, Corynebacteria, Citrobacter, Chlamydia, Brucella, Pseudomonas, Helicobacter,Vibrio.. The recombinant Gram-negative bacterial cell of claim 1 , wherein the bacterial cell is from a genus selected from the group consisting of and6. A ...
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