Nanoparticles displaying fHbp elicit an enhanced antibody response against meningococcal B isolates compared to low valency fHbp antigens

Abstract

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.