ArticlePloS one2012
Monoclonal antibodies to meningococcal factor H binding protein with overlapping epitopes and discordant functional activity.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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16 citing papers in PubMed, 19 citations in OpenAlex.
- Two human antibodies to a meningococcal serogroup B vaccine antigen enhance binding of complement Factor H by stabilizing the Factor H binding site.PLoS pathogens · 2021Article
- 4CMenB vaccine induces elite cross-protective human antibodies that compete with human factor H for binding to meningococcal fHbp.PLoS pathogens · 2020Article
- A stabilized glycomimetic conjugate vaccine inducing protective antibodies against Neisseria meningitidis serogroup A.Nature communications · 2020Article
- Effect of complement Factor H on antibody repertoire and protection elicited by meningococcal capsular group B vaccines containing Factor H binding protein.Human vaccines & immunotherapeutics · 2020Article
- Cocrystal structure of meningococcal factor H binding protein variant 3 reveals a new crossprotective epitope recognized by human mAb 1E6.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019Article
- Structural basis for cooperativity of human monoclonal antibodies to meningococcal factor H-binding protein.Communications biology · 2019Article
- Molecular characterization of two sub-family specific monoclonal antibodies to meningococcal Factor H binding protein.Heliyon · 2018Article
- Human protective response induced by meningococcus B vaccine is mediated by the synergy of multiple bactericidal epitopes.Scientific reports · 2018Article
- Neisseria meningitidis factor H-binding protein bound to monoclonal antibody JAR5: implications for antibody synergy.The Biochemical journal · 2016Article
- Cloning, expression and purification of the factor H binding protein and its interaction with factor H.Iranian journal of microbiology · 2016Article
- Functional Analysis of the Human Antibody Response to Meningococcal Factor H Binding Protein.mBio · 2015Article
- Article
- Review
- Does binding of complement factor H to the meningococcal vaccine antigen, factor H binding protein, decrease protective serum antibody responses?Clinical and vaccine immunology : CVI · 2013Review
- Defining a protective epitope on factor H binding protein, a key meningococcal virulence factor and vaccine antigen.Proceedings of the National Academy of Sciences of the United States of America · 2013Article
- A broadly cross-reactive monoclonal antibody against an epitope on the n-terminus of meningococcal fHbp.Scientific reports · 2012Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
backgroundMeningococcal factor H binding protein (fHbp) is a promising vaccine candidate. Anti-fHbp antibodies can bind to meningococci and elicit complement-mediated bactericidal activity directly. The antibodies also can block binding of the human complement down-regulator, factor H (fH). Without bound fH, the organism would be expected to have increased susceptibility to bacteriolysis. Here we describe bactericidal activity of two anti-fHbp mAbs with overlapping epitopes in relation to their different effects on fH binding and bactericidal activity. METHODS AND PRINCIPAL
findingsBoth mAbs recognized prevalent fHbp sequence variants in variant group 1. Using yeast display and site-specific mutagenesis, binding of one of the mAbs (JAR 1, IgG3) to fHbp was eliminated by a single amino acid substitution, R204A, and was decreased by K143A but not by R204H or D142A. The JAR 1 epitope overlapped that of previously described mAb (mAb502, IgG2a) whose binding to fHbp was eliminated by R204A or R204H substitutions, and was decreased by D142A but not by K143A. Although JAR 1 and mAb502 appeared to have overlapping epitopes, only JAR 1 inhibited binding of fH to fHbp and had human complement-mediated bactericidal activity. mAb502 enhanced fH binding and lacked human complement-mediated bactericidal activity. To control for confounding effects of different mouse IgG subclasses on complement activation, we created chimeric mAbs in which the mouse mAb502 or JAR 1 paratopes were paired with human IgG1 constant regions. While both chimeric mAbs showed similar binding to fHbp, only JAR 1, which inhibited fH binding, had human complement-mediated bactericidal activity.
conclusionsThe lack of human complement-mediated bactericidal activity by anti-fHbp mAb502 appeared to result from an inability to inhibit binding of fH. These results underscore the importance of inhibition of fH binding for anti-fHbp mAb bactericidal activity.
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