Vaccine Medical Development, Scientific and Clinical Affairs, Pfizer Ltd, Tadworth, UK.
Department of Genetics and Genome Biology, University of Leicester, Leicester, UK.
Vaccine. 2020 Nov 17;38(49):7716-7727. doi: 10.1016/j.vaccine.2020.08.031. Epub 2020 Aug 30.
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 can 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.
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。血清群 A、B、C、W 和 Y 是大多数 IMD 病例的病原体，其中血清群 B（MenB）在许多地区导致了相当比例的 IMD 病例。针对血清群 A、C、W 和 Y，已经成功开发了使用荚膜多糖与载体蛋白结合的疫苗。然而，由于 MenB 荚膜多糖的免疫原性较差，因此 MenB 疫苗的开发重点是替代抗原。目前有两种可用的 MenB 疫苗（MenB-4C 和 MenB-FHbp）都包含因子 H 结合蛋白（FHbp），这是一种几乎所有脑膜炎奈瑟菌分离株都携带的表面暴露蛋白，对细菌在人血中的存活至关重要。MenB-4C 除了其他抗原（包括奈瑟菌肝素结合抗原、奈瑟菌黏附素 A 和外膜囊泡）外，还含有来自 B 亚家族的非脂化 FHbp；而 MenB-FHbp 含有来自每个亚家族（A 和 B）的脂化 FHbp。FHbp 具有高度的免疫原性，是两种已许可的 MenB 疫苗所引起的杀菌抗体的主要靶标。FHbp 也是一种重要的疫苗成分，与其他一些可能对菌株间的交叉保护作用有限的脑膜炎球菌抗原不同，因为 FHbp 特异性抗体可以在每个亚家族内提供广泛的交叉保护。亚家族之间的交叉保护作用有限，需要包含来自两个亚家族的 FHbp 变体，以实现广泛的基于 FHbp 的疫苗覆盖。此外，对脂化 FHbp 的免疫反应比非脂化形式的免疫反应具有更好的交叉反应谱。综上所述，包含来自两个 FHbp 亚家族的脂化 FHbp 变体有望提供针对表达广泛 FHbp 序列变体的各种致病脑膜炎球菌菌株的广泛保护。本综述描述了 MenB 疾病预防疫苗的开发，重点介绍了 FHbp 抗原。
