McKechnie Julia L, Kepl Elizabeth, Louth Jennifer, Sun Christina J, Lucidarme Jay, Weatherly Sonia M, Braun Ralph, Feldhaus Andrew, Borrow Ray, Holtzman Douglas
Icosavax, Vaccines & Immune Therapies, BioPharmaceuticals R&D, AstraZeneca, 1930 Boren Ave, Suite 1000, Seattle, WA 98101, USA.
Meningococcal Reference and Vaccine Evaluation Units, UK Health Security Agency, Clinical Sciences Building 2, Manchester Royal Infirmary, Manchester, UK.
Vaccine. 2025 Apr 2;51:126885. doi: 10.1016/j.vaccine.2025.126885. Epub 2025 Feb 20.
Serogroup B meningococcus (MenB) is one of the leading causes of invasive meningococcal disease (IMD) in Western countries. While outbreaks of IMD are rare, this disease can lead to long-term disabilities and even death. These outbreaks typically occur in infants, children, and young adults. There are currently two licensed MenB vaccines: 4CMenB (Bexsero®; GSK Vaccines, Srl, Italy) and MenB-FHbp (Trumenba®, bivalent rLP2086; Pfizer Inc., Collegeville, PA). The effectiveness of these vaccines is dependent upon their ability to elicit a protective antibody response against the various disease-causing strains that are currently circulating. Real-world data has demonstrated that MenB vaccination is effective at preventing IMD. However, it has also been shown that the number of isolates covered by vaccination is limited and can vary from year to year as well as by geographical location. This suggests that a new MenB vaccine which elicits greater breadth of protection would be beneficial. Here we describe the generation of a nanoparticle (NP) displaying a meningococcal factor H-binding protein (fHbp) on its surface. Mice immunized with this fHbp-NP had higher binding antibody titers to both homologous and heterologous fHbp variants compared to mice immunized with low valency fHbp antigens. Importantly, sera from fHbp-NP immunized mice had significantly higher serum bactericidal antibody activity against a range of MenB isolates than mice immunized with low valency antigens or MenB-FHbp. Overall, these studies demonstrate that display of fHbp on nanoparticles elicits a potent and broad antibody response.
B群脑膜炎奈瑟菌(MenB)是西方国家侵袭性脑膜炎球菌病(IMD)的主要病因之一。虽然IMD的暴发很罕见,但这种疾病可导致长期残疾甚至死亡。这些暴发通常发生在婴儿、儿童和年轻人中。目前有两种获得许可的MenB疫苗:4CMenB(Bexsero®;葛兰素史克疫苗公司,意大利)和MenB-FHbp(Trumenba®,二价rLP2086;辉瑞公司,宾夕法尼亚州Collegeville)。这些疫苗的有效性取决于它们引发针对当前流行的各种致病菌株的保护性抗体反应的能力。真实世界的数据表明,MenB疫苗在预防IMD方面是有效的。然而,也已表明,疫苗覆盖的分离株数量有限,并且可能随年份以及地理位置而变化。这表明,一种能引发更广泛保护的新型MenB疫苗将是有益的。在此,我们描述了一种在其表面展示脑膜炎球菌因子H结合蛋白(fHbp)的纳米颗粒(NP)的产生。与用低价fHbp抗原免疫的小鼠相比,用这种fHbp-NP免疫的小鼠对同源和异源fHbp变体具有更高的结合抗体滴度。重要的是,与用低价抗原或MenB-FHbp免疫的小鼠相比,来自fHbp-NP免疫小鼠的血清对一系列MenB分离株具有显著更高的血清杀菌抗体活性。总体而言,这些研究表明,fHbp在纳米颗粒上的展示引发了强效且广泛的抗体反应。