De Staat der Nederlanden; Vert. Door de Minister Van Vws Ministerie Van Volksgezondheid Welzijn en Sport
发明人:
Zariri, Afshin,Pupo Escalona, Elder,Van Der Ley, Peter André
申请号：
AU2017213129
公开号：
AU2017213129A1
申请日:
2017.01.27
申请国别(地区):
AU
年份:
2018
代理人:
摘要：
The present invention relates to neisserial LPS having a hexa-acylated lipid A moiety, wherein the hexa-acylated lipid A moiety is modified as compared to the lipid A moiety of a wild-type neisserial LPS in that it comprises a palmitoleoyl instead of a lauroyl secondary acyl chain on the glucosamine at the non-reducing end of the lipid A moiety. The invention further relates to mixtures of the hexa-acylated LPS with the corresponding penta-acylated LPS, lacking a secondary acyl chain on the glucosamine at the non-reducing end of the lipid A moiety. The invention also relates to neisserial bacteria that have been genetically modified to reduce expression of the endogenous lpxL1geneand to introduce expression of a heterologous thermosensitive lpxP gene for producing the hexa-and penta-acylated LPS. By selecting the time and/or temperature at which the bacterium is grown, it is feasible to increase or decrease the amount of hexa-acylated lipid A structure relative to the corresponding penta-acylated structure and thereby modulate the TLR4 agonist activity of the neisserial LPS of the invention,to the exact level of activity required for a particular immunotherapeutic approach.
