Broad vaccine protection against Neisseria meningitidis using factor H binding protein.
Broad vaccine protection against Neisseria meningitidis using factor H binding protein.
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DOI：
10.1016/j.vaccine.2020.08.031
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发表时间：
2020-11-17
期刊：
影响因子：
5.5
通讯作者：
Balmer P
中科院分区：
文献类型：
--
作者：
Findlow J;Bayliss CD;Beernink PT;Borrow R;Liberator P;Balmer P
脑膜炎奈瑟菌是侵袭性脑膜炎球菌病（IMD）的病原体，根据其多糖荚膜分为不同的血清群。脑膜炎球菌血清群A、B、C、W和Y是大多数IMD病例的原因，血清群B（MenB）在许多地区引起相当大比例的IMD病例。已经成功地开发了使用与载体蛋白缀合的荚膜多糖的疫苗用于血清群A、C、W和Y。然而，由于MenB荚膜多糖的免疫原性差，MenB疫苗的开发集中在替代抗原上。目前可用的两种MenB疫苗（MenB-4C和MenB-FHbp）都包含因子H结合蛋白（FHbp），这是一种表面暴露的蛋白质，几乎所有脑膜炎球菌分离株都含有这种蛋白质，它对细菌在人类血液中的存活非常重要。MenB-4 C含有来自亚家族B的非脂化FHbp以及其他抗原，包括奈瑟球菌肝素结合抗原、奈瑟球菌粘附素A和外膜囊泡，而MenB-FHbp含有来自每个亚家族（A和B）的脂化FHbp。FHbp是高度免疫原性的，并且是由两种许可的MenB疫苗引发的抗体的杀菌活性的主要靶标。FHbp也是一种重要的疫苗成分，与其他一些脑膜炎球菌抗原不同，这些抗原在菌株之间可能具有有限的交叉保护，因为FHbp特异性抗体在每个亚家族内提供广泛的交叉保护。亚家族之间有限的交叉保护需要包括来自两个亚家族的FHbp变体以实现广泛的基于FHbp的疫苗覆盖。此外，对脂化形式的FHbp的免疫应答具有上级由非脂化形式引起的交叉反应特征。总之，预期包含来自两个FHbp亚家族的脂化FHbp变体提供针对表达广泛FHbp序列变体的多种致病脑膜炎球菌菌株的广泛保护。本文综述了MenB疾病预防疫苗的发展，重点是FHbp抗原。
Neisseria meningitidis, the causative agent of invasive meningococcal disease (IMD), is classified into different serogroups defined by their polysaccharide capsules. Meningococcal serogroups A, B, C, W, and Y are responsible for most IMD cases, with serogroup B (MenB) causing a substantial percentage of IMD cases in many regions. Vaccines using capsular polysaccharides conjugated to carrier proteins have been successfully developed for serogroups A, C, W, and Y. However, because the MenB capsular polysaccharide is poorly immunogenic, MenB vaccine development has focused on alternative antigens. The 2 currently available MenB vaccines (MenB-4C and MenB-FHbp) both include factor H binding protein (FHbp), a surface-exposed protein harboured by nearly all meningococcal isolates that is important for survival of the bacteria in human blood. MenB-4C contains a nonlipidated FHbp from subfamily B in addition to other antigens, including Neisserial Heparin Binding Antigen, Neisserial adhesin A, and outer membrane vesicles, whereas MenB-FHbp contains a lipidated FHbp from each subfamily (A and B). FHbp is highly immunogenic and a main target of bactericidal activity of antibodies elicited by both licensed MenB vaccines. FHbp is also an important vaccine component, in contrast to some other meningococcal antigens that may have limited cross-protection across strains, as FHbp-specific antibodies provide broad cross-protection within each subfamily. Limited cross-protection between subfamilies necessitates the inclusion of FHbp variants from both subfamilies to achieve broad FHbp-based vaccine coverage. Additionally, immune responses to the lipidated form of FHbp have a superior cross-reactive profile to those elicited by the nonlipidated form. Taken together, the inclusion of lipidated FHbp variants from both FHbp subfamilies is expected to provide broad protection against the diverse disease-causing meningococcal strains expressing a wide range of FHbp sequence variants. This review describes the development of vaccines for MenB disease prevention, with a focus on the FHbp antigen.
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