专利名称 | The modified hexa- acyl-Neisseria LPS | ||
申请号 | JP2018538644 | 申请日 | |
公开(公告)号 | JP2019503424A | 公开(公告)日 | 2017-01-27 |
申请(专利权)人 | 发明人 | ザリリ アフシン; プポ エスカローナ エルダー; ヴァン ダー レイ ピーター アンドレ | |
专利来源 | 国家知识产权局 | 转化方式 | |
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 lpxL1 gene and 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. |
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