title: Serum Bactericidal Antibody Responses of Adults Immunized with the MenB-4C Vaccine against Genetically Diverse Serogroup B Meningococci.
abstract: MenB-4C is a meningococcal vaccine for the prevention of serogroup B disease. The vaccine contains factor H binding protein (FHbp) and three other antigens that can elicit serum bactericidal antibodies (SBA). For vaccine licensure, efficacy was inferred from the SBA responses against three antigen-specific indicator strains. The relation between those results and broad protection against circulating genetically diverse strains is not known. Twenty adults were immunized with two doses of MenB-4C given 1 to 2 months apart. SBA activity against 3 reference strains and 15 serogroup B test strains (6 from college outbreaks) was measured. Compared to the preimmunization titers, 70%, 95%, and 95% of subjects had ≥4-fold increases in the titers of anti-PorA P1.4, anti-NadA, and anti-FHbp antibodies against the reference strains, respectively. In contrast, only 25 to 45% of the subjects had ≥4-fold increases in responses to 10 of the 15 test strains, including 8 that expressed one to three of the antigens in the vaccine. At 1 month, the majority of subjects with <4-fold titer increases had serum titers of ≥1:4, which are considered sufficient for protection. However, the titers against four strains declined to <1:4 by 4 to 6 months in one-third to greater than 50% of the subjects tested. Clinically relevant isolates are often more resistant to SBA than the indicator strains used to measure antigen-specific SBA. A working model is that the percentage of subjects with titers of ≥1:4 at 1 month postimmunization correlates with short-term protection against that strain, whereas the percentage of subjects with ≥4-fold titer increases represents a more robust response. (The protocol used at the Oxford Vaccine Group has been registered at ClinicalTrials.gov under registration no. NCT02398396.).
authors.affiliation: Center for Immunobiology and Vaccine Development, UCSF Benioff Children's Hospital Oakland, Oakland, California, USA.
authors.forename: Serena
authors.initials: S
authors.lastname: Giuntini
authors.affiliation: Center for Immunobiology and Vaccine Development, UCSF Benioff Children's Hospital Oakland, Oakland, California, USA.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Lujan
authors.affiliation: Oxford Vaccine Group, Department of Paediatrics, University of Oxford, and the NIHR Oxford Biomedical Research Centre, Oxford, United Kingdom.
authors.forename: Malick M
authors.initials: MM
authors.lastname: Gibani
authors.affiliation: Oxford Vaccine Group, Department of Paediatrics, University of Oxford, and the NIHR Oxford Biomedical Research Centre, Oxford, United Kingdom.
authors.forename: Christina
authors.initials: C
authors.lastname: Dold
authors.affiliation: Oxford Vaccine Group, Department of Paediatrics, University of Oxford, and the NIHR Oxford Biomedical Research Centre, Oxford, United Kingdom.
authors.forename: Christine S
authors.initials: CS
authors.lastname: Rollier
authors.affiliation: Oxford Vaccine Group, Department of Paediatrics, University of Oxford, and the NIHR Oxford Biomedical Research Centre, Oxford, United Kingdom.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Pollard
authors.affiliation: Center for Immunobiology and Vaccine Development, UCSF Benioff Children's Hospital Oakland, Oakland, California, USA dgranoff@chori.org.
authors.forename: Dan M
authors.initials: DM
authors.lastname: Granoff
mesh_terms: D000328:Adult; D000917:Antibody Formation; D001770:Blood Bactericidal Activity; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D022401:Meningococcal Vaccines / Q000008:administration & dosage* / Q000276:immunology*; D038541:Neisseria meningitidis, Serogroup B / Q000145:classification / Q000235:genetics / Q000276:immunology*; D055815:Young Adult
chemical_list: C570015:4CMenB vaccine; D022401:Meningococcal Vaccines
keywords: Bexsero; FH; FHbp; MenB-4C; autoantibody; complement factor H; factor H binding protein; meningococcal vaccine