van der Ley Peter, van den Dobbelsteen Germie
Unit Vaccinology, National Institute of Public Health and the Environment (RIVM), Bilthoven, The Netherlands.
Hum Vaccin. 2011 Aug;7(8):886-90. doi: 10.4161/hv.7.8.16086. Epub 2011 Aug 1.
Outer membrane vesicles (OMVs) have been used extensively as experimental vaccines against Neisseria meningitidis. Classical meningococcal OMV vaccines contain wildtype lipopolysaccharide (LPS) with a hexa-acylated lipid A moiety, which is a very potent activator of the TLR4 receptor. While this may make the LPS an effective "internal" adjuvant, it also contributes to vaccine reactogenicity. Reduction of endotoxic activity has therefore been essential for the application of meningococcal OMV vaccines in humans. Classical OMV vaccines have a reduced LPS content as a result of detergent extraction, mostly with deoxycholate. An alternative method is the use of meningococcal strains with genetically detoxified LPS, in particular where mutation in the lpxL1 gene has resulted in penta-acylated lipid A with strongly attenuated endotoxic activity. This allows the use of native OMVs without any need for LPS removal by detergent extraction, making it a much easier to produce and more versatile vaccine platform. Several groups have now started the development of native OMV vaccines based on non-toxic LPS mutants, and this Commentary provides an overview of the various approaches and results thus far.
外膜囊泡（OMV）已被广泛用作抗脑膜炎奈瑟菌的实验性疫苗。经典的脑膜炎球菌OMV疫苗含有带有六酰化脂质A部分的野生型脂多糖（LPS），这是TLR4受体的一种非常有效的激活剂。虽然这可能使LPS成为一种有效的“内部”佐剂，但它也会导致疫苗的反应原性。因此，降低内毒素活性对于脑膜炎球菌OMV疫苗在人类中的应用至关重要。经典的OMV疫苗由于用去污剂（主要是脱氧胆酸盐）提取而使LPS含量降低。另一种方法是使用具有基因解毒LPS的脑膜炎球菌菌株，特别是在lpxL1基因发生突变导致五酰化脂质A且内毒素活性大大减弱的情况下。这使得可以使用天然的OMV，而无需通过去污剂提取去除LPS，从而使其成为一个更容易生产且更通用的疫苗平台。现在有几个研究小组已经开始基于无毒LPS突变体开发天然OMV疫苗，本述评概述了迄今为止的各种方法和结果。
