Neisseria meningitidis factor H binding protein – human factor H interface (fHbp–fH interface)

The Neisseria meningitidis factor H binding protein (fHbp) – human factor H (fH) interface is a critical molecular interaction that allows the meningococcus to evade the human innate immune system. fHbp is a surface-exposed lipoprotein that recruits human fH, a negative regulator of the alternative complement pathway, to the bacterial surface (Schneider et al., 2009, Nature). This recruitment prevents the deposition of C3b and subsequent formation of the membrane attack complex, thereby protecting the bacteria from lysis and opsonophagocytosis (Madico et al., 2006, Journal of Immunology). This interface is the primary target for recombinant protein-based vaccines such as Trumenba (MenB-fHbp) and Bexsero (4CMenB), which induce antibodies that block fH binding and trigger complement-mediated killing (Pizza et al., 2020, Science Translational Medicine). A significant challenge in targeting this interface is the high degree of sequence variability in fHbp, which is categorized into three main variants or two subfamilies (Masignani et al., 2003, Journal of Experimental Medicine). Effective therapeutic and preventive strategies must account for this diversity to ensure broad protection against various meningococcal strains.

Other names

fHbpGNA1870LP2086Factor H binding proteinMeningococcal factor H binding proteinGenome-derived Neisseria Antigen 1870

Induction of bactericidal antibodies that competitively inhibit the binding of human factor H to fHbp and/or activate the classical complement pathway (FDA, 2014, Trumenba Prescribing Information).