Section of Microbiology, Department of Medicine, Imperial College London, London, UK.
Vaccine. 2011 Sep 16;29(40):6858-65. doi: 10.1016/j.vaccine.2011.07.060. Epub 2011 Jul 29.
Because meningitis and septicaemia caused by Neisseria meningitidis are major public health problems worldwide, the design of a broadly protective vaccine remains a priority. Type IV pili (Tfp) are surface-exposed filaments playing a key role in pathogenesis in a variety of bacterial species, including N. meningitidis, that have demonstrated vaccine potential. Unfortunately, in the meningococcus, the major pilus subunit PilE usually undergoes extensive antigenic variation and is therefore not suitable as a vaccine component. However, we have recently shown that N. meningitidis Tfp contain low abundance subunits PilX, PilV and ComP, collectively called minor pilins, that are highly conserved and modulate Tfp-linked functions key to pathogenesis. This prompted us to examine the vaccine potential of these proteins by assessing whether sera directed against them have bactericidal properties and/or are able to interfere with Tfp-linked functions. Here we show that minor pilin proteins are recognized by sera of patients convalescent from meningococcal disease and that antibodies directed against some of them can selectively interfere with Tfp-linked functions. This shows that, despite their apparent inability to elicit bactericidal antibodies, minor pilins might have vaccine potential.
由于脑膜炎奈瑟菌引起的脑膜炎和败血症是全球主要的公共卫生问题,因此设计一种广泛保护的疫苗仍然是当务之急。IV 型菌毛(Tfp)是一种表面暴露的丝状体,在多种细菌中发挥着关键作用,包括脑膜炎奈瑟菌,这些细菌具有疫苗潜力。不幸的是,在脑膜炎奈瑟菌中,主要菌毛亚基 PilE 通常经历广泛的抗原变异,因此不适合作为疫苗成分。然而,我们最近表明,脑膜炎奈瑟菌 Tfp 包含低丰度的亚基 PilX、PilV 和 ComP,统称为次要菌毛,它们高度保守,并调节与菌毛相关的对发病机制至关重要的功能。这促使我们通过评估针对这些蛋白的血清是否具有杀菌特性和/或能够干扰与菌毛相关的功能来研究这些蛋白的疫苗潜力。在这里,我们表明,来自脑膜炎球菌病恢复期患者的血清可以识别次要菌毛蛋白,并且针对其中一些蛋白的抗体可以选择性地干扰与菌毛相关的功能。这表明,尽管它们显然不能引发杀菌抗体,但次要菌毛可能具有疫苗潜力。