Publications by authors named "D W Granoff"

Article Synopsis
  • Six cases of serogroup B meningococcal disease were reported among individuals who had received either the MenB-4C or MenB-FHbp vaccines in the U.S. since their availability.
  • All cases were investigated through health records and whole genome sequencing, revealing that most patients were at higher risk due to either outbreaks or pre-existing medical conditions.
  • Factors such as incomplete vaccination, waning immunity, and strain resistance to vaccine-induced serum bactericidal activity (SBA) played significant roles in the occurrence of these cases.
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Factor H binding protein (FHbp) is an important virulence factor that binds a negative regulator of the alternative complement pathway, human factor H (FH). Binding of FH increases meningococcal resistance to complement-mediated killing. FHbp also is reported to prevent interaction of the antimicrobial peptide (AMP) LL-37 with the meningococcal surface and meningococcal killing.

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Meningococcal serogroup B (MenB) vaccines contain recombinant factor H binding protein (FHbp), which can complex with complement factor H (CFH) and thereby risk eliciting anti-FH autoantibodies. While anti-FH antibodies can be present in sera of healthy persons, the antibodies are implicated in autoimmune atypical hemolytic uremic syndrome and C3 glomerulopathies. We immunized 120 students with a MenB vaccine (Bexsero).

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MenB-4C (Bexsero; GlaxoSmithKline Biologicals) is a licensed meningococcal vaccine for capsular B strains. The vaccine contains detergent-extracted outer membrane vesicles (dOMV) and three recombinant proteins, of which one is factor H binding protein (FHbp). In previous studies, overexpression of FHbp in native OMV (NOMV) with genetically attenuated endotoxin (LpxL1) and/or by the use of mutant FHbp antigens with low factor H (FH) binding increased serum bactericidal antibody (SBA) responses.

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