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基于乳酸奈瑟菌外膜囊泡的脑膜炎球菌病疫苗的研发。

The development of a meningococcal disease vaccine based on Neisseria lactamica outer membrane vesicles.

作者信息

Gorringe Andrew, Halliwell Denise, Matheson Mary, Reddin Karen, Finney Michelle, Hudson Michael

机构信息

Health Protection Agency, Porton Down, Salisbury SP4 0JG, UK.

出版信息

Vaccine. 2005 Mar 18;23(17-18):2210-3. doi: 10.1016/j.vaccine.2005.01.055.

Abstract

Serogroup B meningococcal disease remains a serious problem in many countries and no effective vaccine is currently available. Immunological and epidemiological evidence suggests that carriage of commensal Neisseria species is involved in the development of natural immunity against meningococcal disease. Neisseria lactamica has many surface structures in common with Neisseria meningitidis and may be the most important of these species. We have produced extensive pre-clinical data, which indicate that N. lactamica outer membrane vesicles (OMVs) may provide a vaccine effective against diverse disease-causing meningococcal strains. Immunisation with N. lactamica OMVs protected against lethal challenge with diverse meningococcal isolates in a mouse intraperitoneal challenge model of meningococcal disease and we are developing this vaccine for use in a phase I safety and immunogenicity study in adult volunteers. We have shown that OMVs produced from bacteria grown under iron-limited or iron-rich conditions provide equivalent protection in the mouse infection model and thus OMVs produced from iron-rich will be used. Sterile filtration of N. lactamica OMVs has proved difficult but this has been improved by resuspending the vesicles in a buffer, which increases their surface zeta potential. The vaccine is currently being manufactured and validated ELISA protocols have been developed for the analysis of serological responses.

摘要

B 群脑膜炎球菌病在许多国家仍然是一个严重问题,目前尚无有效的疫苗。免疫学和流行病学证据表明,共生奈瑟菌的携带与针对脑膜炎球菌病的天然免疫力的发展有关。乳酸奈瑟菌与脑膜炎奈瑟菌有许多共同的表面结构,可能是这些菌种中最重要的。我们已经产生了大量临床前数据,表明乳酸奈瑟菌外膜囊泡(OMV)可能提供一种对多种致病性脑膜炎球菌菌株有效的疫苗。在脑膜炎球菌病的小鼠腹腔攻击模型中,用乳酸奈瑟菌 OMV 免疫可保护小鼠免受多种脑膜炎球菌分离株的致命攻击,我们正在开发这种疫苗用于成年志愿者的 I 期安全性和免疫原性研究。我们已经表明,在铁限制或铁丰富条件下生长的细菌产生的 OMV 在小鼠感染模型中提供同等保护,因此将使用铁丰富条件下产生的 OMV。乳酸奈瑟菌 OMV 的无菌过滤已证明很困难,但通过将囊泡重悬于缓冲液中得到了改善,这增加了它们的表面zeta 电位。目前正在生产该疫苗,并且已经开发出经过验证的 ELISA 方案用于分析血清学反应。

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