DE STAAT DER NEDERLANDEN; VERT. DOOR DE MINISTER VAN VWS; WELZIJN EN SPORT; MINISTERIE VAN VOLKSGEZONDHEID
发明人:
ZARIRI, AFSHIN,PUPO ESCALONA, ELDER,VAN DER LEY, PETER ANDRE
申请号：
CA3011284
公开号：
CA3011284A1
申请日:
2017.01.27
申请国别(地区):
CA
年份:
2017
代理人:
摘要：
The present invention relates to neisserial LPS having a hexa-acylated lipid Amoiety, wherein the hexa-acylated lipidA moiety is modified as compared to the lipid A moiety of a wild-typeneisserial LPS in that it comprises a palmitoleoyl instead ofa lauroyl secondary acyl chain on the glucosamine at the non-reducing end ofthe lipid A moiety. The invention further relates tomixtures of the hexa-acylated LPS with the corresponding penta-acylated LPS,lacking a secondary acyl chain on the glucosamine atthe non-reducing end of the lipid A moiety. The invention also relates toneisserial bacteria that have been genetically modified to reduceexpression of the endogenous 1pxL1geneand to introduce expression of aheterologous thermosensitive 1pxP gene for producingthe hexa-and penta-acylated LPS. By selecting the time and/or temperature atwhich the bacterium is grown, it is feasible to increaseor decrease the amount of hexa-acylated lipid A structure relative to thecorresponding penta-acylated structure and therebymodulate the TLR4 agonist activity of the neisserial LPS of the invention,tothe exact level of activity required for a particular immunotherapeuticapproach.
