title: Effect of complement Factor H on anti-FHbp serum bactericidal antibody responses of infant rhesus macaques boosted with a licensed meningococcal serogroup B vaccine.
abstract: FHbp is a major serogroup B meningococcal vaccine antigen. Binding of complement Factor H (FH) to FHbp is specific for human and some non-human primate FH. In previous studies, FH binding to FHbp vaccines impaired protective anti-FHbp antibody responses. In this study we investigated anti-FHbp antibody responses to a third dose of a licensed serogroup B vaccine (MenB-4C) in infant macaques vaccinated in a previous study with MenB-4C. Six macaques with high binding of FH to FHbp (FH(high)), and six with FH(low) baseline phenotypes, were immunized three months after dose 2. After dose 2, macaques with the FH(low) baseline phenotype had serum anti-FHbp antibodies that enhanced FH binding to FHbp (functionally converting them to a FH(high) phenotype). In this group, activation of the classical complement pathway (C4b deposition) by serum anti-FHbp antibody, and anti-FHbp serum bactericidal titers were lower after dose 3 than after dose 2 (p<0.02). In macaques with the FH(high) baseline phenotype, the respective anti-FHbp C4b deposition and bactericidal titers were similar after doses 2 and 3. Two macaques developed serum anti-FH autoantibodies after dose 2, which were not detected after dose 3. In conclusion, in macaques with the FH(low) baseline phenotype whose post-dose 2 serum anti-FHbp antibodies had converted them to FH(high), the anti-FHbp antibody repertoire to dose 3 was skewed to less protective epitopes than after dose 2. Mutant FHbp vaccines that eliminate FH binding may avoid eliciting anti-FHbp antibodies that enhance FH binding, and confer greater protection with less risk of inducing anti-FH autoantibodies than FHbp vaccines that bind FH.
authors.affiliation: Center for Immunobiology and Vaccine Development, UCSF Benioff Children's Hospital Oakland, 5700 Martin Luther King Jr. Way, Oakland, CA 94609, United States.
authors.forename: Serena
authors.initials: S
authors.lastname: Giuntini
authors.affiliation: Center for Immunobiology and Vaccine Development, UCSF Benioff Children's Hospital Oakland, 5700 Martin Luther King Jr. Way, Oakland, CA 94609, United States.
authors.forename: Peter T
authors.initials: PT
authors.lastname: Beernink
authors.affiliation: Center for Immunobiology and Vaccine Development, UCSF Benioff Children's Hospital Oakland, 5700 Martin Luther King Jr. Way, Oakland, CA 94609, United States. Electronic address: dgranoff@chori.org.
authors.forename: Dan M
authors.initials: DM
authors.lastname: Granoff
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000907:Antibodies, Bacterial / Q000276:immunology*; D000942:Antigens, Bacterial / Q000276:immunology*; D001426:Bacterial Proteins / Q000276:immunology*; D001770:Blood Bactericidal Activity; D017242:Complement Factor H / Q000378:metabolism*; D007117:Immunization, Secondary; D008253:Macaca mulatta; D022401:Meningococcal Vaccines / Q000008:administration & dosage / Q000276:immunology*
chemical_list: C570015:4CMenB vaccine; D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D022401:Meningococcal Vaccines; C484699:factor H-binding protein, Neisseria meningitidis; D017242:Complement Factor H
keywords: 4CMenB; Bexsero(®); Complement; Factor H; Factor H binding protein; Neisseria meningitidis; Non-human primate; Vaccine