ДЕ СТАТ ДЕР НЕДЕРЛАНДЕН; ВЕРТ. ДОР ДЕ МИНИСТЕР ВАН ВВС (NL)
发明人:
ВАН ДЕ ВАТЕРБЕМД Бас (NL),ВАН ДЕР ПОЛ Леонардус Адольфус (NL)
申请号：
RU2014104241/10
公开号：
RU2014104241A
申请日:
2012.07.05
申请国别(地区):
RU
年份:
2015
代理人:
摘要：
1. A method of producing bezdetergentnogo bacterial outer membrane vesicle (OMV) for use in vaccines, comprising the steps of: a) culturing a population of gram-negative bacteria to stationary growth phase b) at the time of at least about 1 hour after the start of the stationary phase of growth bacteria incubation obtained in step a), in a medium with adjusted pH value available or higher than 8.0 and having a concentration of the metal chelating agent, preferably EDTA, from about 1 to 100 mM, for OMV extraction and, c) OMV extraction extracted in step b), where the extraction comprises at least the removal of bacteria from OMV.2. The method of claim 1, wherein the gram-negative bacterium is genetically modified, through which the bacterium produces LPS with reduced toxicity, but this LPS retains at least part of its adjuvant activity preferably, said genetic modification is a modification that reduces or completely suppress expression of one or more genes selected from genes lpxL1 and lpxL2 or their homologues and gene lpxK or homologues and / or a modification that renders the influence of the expression of one or lpxE more genes and / or pagL.3. The method of claim 1, wherein the time after the start of the stationary growth phase, during which the bacteria are incubated in the medium in step b), is from about 1 to 9 hours, more preferably from about 2 to 5 p.4. The method of claim 1, wherein the OMV sterilized, preferably by sterilizing filtration, preferably using a filter with a pore size of less than about 0.3 mkm.5. The method of claim 1, wherein a1. Способ бездетергентного получения бактериальных везикул наружной мембраны (OMV) для использования в вакцинах, включающий стадии:a) культивирования популяции грамотрицательных бактерий до фазы стационарного ростаb) в момент времени по меньшей мере примерно через 1 ч после начала фазы стационарного роста инкубацию бактерий, полученных на стадии a), в среде с доведенным или имеющимся значением pH выше 8,0 и имеющей
