Role of Factor H Binding Protein in Neisseria meningitidis Virulence and Its Potential as a Vaccine Candidate To Broadly Protect against Meningococcal Disease

Abstract

SUMMARY Neisseria meningitidis is a Gram-negative microorganism that exists exclusively in humans and can cause devastating invasive disease. Although capsular polysaccharide-based vaccines against serogroups A, C, Y, and W135 are widely available, the pathway to a broadly protective vaccine against serogroup B has been more complex. The last 11 years has seen the discovery and development of the N. meningitidis serogroup B (MnB) outer membrane protein factor H binding protein (fHBP) as a vaccine component. Since the initial discovery of fHBP, a tremendous amount of work has accumulated on the diversity, structure, and regulation of this important protein. fHBP has proved to be a virulence factor for N. meningitidis and a target for functional bactericidal antibodies. fHBP is critical for survival of meningococci in the human host, as it is responsible for the primary interaction with human factor H (fH). Binding of hfH by the meningococcus serves to downregulate the host alternative complement pathway and helps the organism evade host innate immunity. Preclinical studies have shown that an fHBP-based vaccine can elicit serum bactericidal antibodies capable of killing MnB, and the vaccine has shown very encouraging results in human clinical trials. This report reviews our current knowledge of fHBP. In particular, we discuss the recent advances in our understanding of fHBP, its importance to N. meningitidis , and its potential role as a vaccine for preventing MnB disease.

The Dual Role of Lipids of the Lipoproteins in Trumenba, a Self-Adjuvanting Vaccine Against Meningococcal Meningitis B Disease

“…B24 is found in 43.8% and 16.7% of invasive NmB strains in the USA and Europe, respectively (13). Thus, additional non-fHbp components were included in Bexsero to extend the coverage of the vaccine to other strains (14). Trumenba contains two lipidated fHbp variants, one from subfamily A (variant A05) and one from subfamily B (variant B01).…”

Heterogeneity in Rhesus Macaque Complement Factor H Binding to Meningococcal Factor H Binding Protein (FHbp) Informs Selection of Primates To Assess Immunogenicity of FHbp-Based Vaccines

“…This vaccine is licensed in the European Union, Australia, and Canada. Another serogroup B vaccine that contains FHbp is in late-stage clinical development by Pfizer Vaccines (2). FHbp was referred to as GNA 1870 (3) or LP2086 (4) when our laboratories discovered that an important function of this protein was to bind complement factor H (FH) to the bacterial surface and downregulate complement activation (5).…”

Recombinant Protein Truncation Strategy for Inducing Bactericidal Antibodies to the Macrophage Infectivity Potentiator Protein of Neisseria meningitidis and Circumventing Potential Cross-Reactivity with Human FK506-Binding Proteins

“…Estimating the breadth of strain coverage afforded by the bivalent rLP2086 vaccine is a complex task, but, using a methodology based on a killing assay, it has been reported that for toddlers and adolescents-young adults, protective bactericidal titers ranged from 44% to 100% and from 68% to 98%, respectively, against MenB strains expressing heterologous fHbp proteins (17).…”