中文摘要：本发明主要涉及一种基因工程菌，尤其是利用基因工程改造后的大肠杆菌制备重组O-抗原连接酶以及一种新型脂多糖分子，并公开了生产这种新型脂多糖分子的方法及其应用。本发明同时公开了包含这种脂多糖或源于重组O型抗原连接酶的脂多糖衍生物的疫苗佐剂，这种佐剂可用于调节机体免疫反应，提高机体抗生素敏感性，提高疫苗的适应性和亲和力，且无毒无害。
 
外文摘要：The present disclosure generally relates to genetic engineering of bacteria. More particularly, the present disclosure describes genetic engineering of E. coli to create mutant O-antigen ligase, as well as novel lipopolysaccharide molecules resulting from that genetic engineering. Methods for using those novel molecules are also described.
NOVELTY - Vaccine adjuvant comprises a lipopolysaccharide (LPS) or its derivative isolated from a mutant O-antigen ligase. The mutant O-antigen ligase is chosen from mutant O-antigen ligase comprising isolated protein having a 419 amino acid sequence (SEQ ID NO: 1) fully defined in the specification and mutant O-antigen ligase comprising isolated protein having at least 90% sequence identity to a 419 amino acid sequence (SEQ ID NO: 2) fully defined in the specification and having amino acid substitution of phenylalanine to serine at phenylalanine homologous to position 332 of SEQ ID NO: 2.
USE - The vaccine adjuvant is used for stimulating immune response.
ADVANTAGE - The vaccine adjuvant has increased antibiotic sensitivity, is non-toxic, and has improved compatibility and binding affinity.
 
主权项：DETAILED DESCRIPTION - Vaccine adjuvant comprises (a) at least one lipopolysaccharide (LPS) or its derivative isolated from a mutant O-ant! igen ligase. The mutant O-antigen ligase is chosen from a mutant O-antigen ligase comprising an isolated protein having a 419 amino acid sequence (SEQ ID NO: 1) fully defined in the specification and mutant O-antigen ligase comprising an isolated protein having at least 90% sequence identity to a 419 amino acid sequence (SEQ ID NO: 2) fully defined in the specification and having an amino acid substitution of phenylalanine to serine at the phenylalanine homologous to position 332 of SEQ ID NO: 2, where the protein has at least one of O-antigen ligase activity or the activity to ligate lipid A to disaccharide pentapeptide (DPP), or (b) a LPS derivative molecule prepared by (i) providing an Escherichia coli strain adapted to express a LPS derivative molecule having reduced endotoxicity compared to a LPS molecule that the LPS derivative is derived from, (ii) modifying the E.coli strain by creating the above-mentioned mutant O-antigen ligase, and (iii) allowing the modified E.c! oli strain to grow under conditions to produce a LPS-1 derivat! ive (LPS glycoform) molecule having reduced endotoxicity and improved immunogenicity as compared to the LPS molecule or its derivative from which it is produced. INDEPENDENT CLAIMS are included for the following:
(1) LPS glycoform modified with peptidoglycan cell wall fragments; and
(2) a modified lipopolysaccharide molecule having at least one non-native sugar and a greater molecular weight as compared to the lipopolysaccharide molecule from which it is modified.
 
申请号：US201715586781
公开/公告号：US2017239350A1
申请日：2017-05-04
公开/公告日：2017-08-24
申请/专利权人：UNIV PRINCETON (UPRT-C)
发明/设计人：SILHAVY, T J;GRABOWICZ, M; KAHNE, D; LEBAR, M; ANDRES, D
分类号：A61K39/39; C07H13/06; C07H15/04; C07K4/00; C12N15/04; C12N9/00; C12N9/93; C12P21/005; A61K2039/55516; A61K2039/55572; A61K2039/55583; A61K2039/55594
主分类号：A61K39/39; C07H13/06; C12N15/04; C12N9/00; C12P21/00
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