Sequence conservation of pilus subunits in Neisseria meningitidis

Sequence conservation of pilus subunits in Neisseria meningitidis
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DOI:
10.1016/j.vaccine.2010.04.065
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发表时间:
2010-07-05
期刊:
影响因子:
5.5
通讯作者:
Pelicic, Vladimir
Pelicic, Vladimir
中科院分区:
医学3区
文献类型:
--
作者:
Cehovin, Ana;Winterbotham, Megan;Pelicic, Vladimir

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脑膜炎奈瑟氏菌感染的快速发病和严重后果使得设计广泛保护性疫苗成为公共卫生的优先事项。人们一直在寻找表面暴露、广泛保守并能诱导保护性抗体的脑膜炎球菌组分。IV型皮利(Tfp)是丝状结构,在发病机制中发挥关键作用,延伸到细菌表面之外,并已证明具有疫苗潜力。然而,PilE(Tfp的主要亚基)的广泛抗原变异意味着它们目前被认为是不合适的疫苗组分。最近已经显示,除了PilE之外,Tfp还含有低丰度的菌毛蛋白ComP、PilV和PilX。这促使我们在一组N.脑膜炎病毒分离株。我们发现,所有的次要菌毛蛋白是高度保守的,主要菌毛蛋白基因也高度保守的ST-8和ST-11克隆复合物。这些数据具有重要的意义,重新考虑菌毛亚单位作为疫苗抗原。(C)2010爱思唯尔有限公司版权所有。
The rapid onset and dramatic consequences of Neisseria meningitidis infections make the design of a broadly protective vaccine a priority for public health. There is an ongoing quest for meningococcal components that are surface exposed, widely conserved and can induce protective antibodies. Type IV pili (Tfp) are filamentous structures with a key role in pathogenesis that extend beyond the surface of the bacteria and have demonstrated vaccine potential. However, extensive antigenic variation of PilE, the major subunit of Tfp, means that they are currently considered to be unsuitable vaccine components. Recently it has been shown that Tfp also contain low abundance pilins ComP, PilV and PilX in addition to PilE. This prompted us to examine the prevalence and sequence diversity of these proteins in a panel of N. meningitidis disease isolates. We found that all minor pilins are highly conserved and the major pilin genes are also highly conserved within the ST-8 and ST-11 clonal complexes. These data have important implications for the re-consideration of pilus subunits as vaccine antigens. (C) 2010 Elsevier Ltd. All rights reserved.