title: Susceptibility of Meningococcal Strains Responsible for Two Serogroup B Outbreaks on U.S. University Campuses to Serum Bactericidal Activity Elicited by the MenB-4C Vaccine.
abstract: In 2013 and 2014, two U.S. universities had meningococcal serogroup B outbreaks (a total of 14 cases) caused by strains from two different clonal complexes. To control the outbreaks, students were immunized with a serogroup B meningococcal vaccine (Novartis) that was not yet licensed in the United States. The vaccine (referred to as MenB-4C) contains four components capable of eliciting bactericidal activity. Both outbreak strains had high expression levels of two of the vaccine antigens (subfamily B factor H binding protein [FHbp] and neisserial heparin binding antigen [NHba]); the university B outbreak strain also had moderate expression of a third antigen, NadA. We investigated the bactericidal activity of sera from mice immunized with FHbp, NHba, or NadA and sera from MenB-4C-immunized infant macaques and an adult human. The postimmunization bactericidal activity of the macaque or human serum against isolates from university B with FHbp identification (ID) 1 that exactly matched the vaccine FHbp sequence variant was 8- to 21-fold higher than that against isolates from university A with FHbp ID 276 (96% identity to the vaccine antigen). Based on the bactericidal activity of mouse antisera to FHbp, NadA, or NHba and macaque or human postimmunization serum that had been depleted of anti-FHbp antibody, the bactericidal activity against both outbreak strains largely or entirely resulted from antibodies to FHbp. Thus, despite the high level of strain expression of FHbp from a subfamily that matched the vaccine antigen, there can be large differences in anti-FHbp bactericidal activity induced by MenB-4C vaccination. Further, strains with moderate to high NadA and/or NHba expression can be resistant to anti-NadA or anti-NHba bactericidal activity elicited by MenB-4C vaccination.
authors.affiliation: Center for Immunobiology and Vaccine Development, UCSF Benioff Children's Hospital Oakland, Oakland, California, USA.
authors.forename: Raffaella
authors.initials: R
authors.lastname: Rossi
authors.affiliation: Center for Immunobiology and Vaccine Development, UCSF Benioff Children's Hospital Oakland, Oakland, California, USA.
authors.forename: Peter T
authors.identifier: http://orcid.org/0000-0001-5734-083X
authors.initials: PT
authors.lastname: Beernink
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 dgranoff@chori.org.
authors.forename: Dan M
authors.initials: DM
authors.lastname: Granoff
mesh_terms: D018829:Adhesins, Bacterial / Q000235:genetics / Q000276:immunology; D000328:Adult; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D000942:Antigens, Bacterial / Q000235:genetics / Q000276:immunology; D001426:Bacterial Proteins / Q000276:immunology; D001770:Blood Bactericidal Activity; D006801:Humans; D008253:Macaca mulatta; D008589:Meningococcal Infections / Q000453:epidemiology / Q000276:immunology* / Q000382:microbiology / Q000517:prevention & control; D022401:Meningococcal Vaccines / Q000008:administration & dosage / Q000276:immunology*; D051379:Mice; D038541:Neisseria meningitidis, Serogroup B / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification; D014481:United States / Q000453:epidemiology; D014495:Universities
chemical_list: C570015:4CMenB vaccine; D018829:Adhesins, Bacterial; D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D022401:Meningococcal Vaccines; C501982:NadA protein, Neisseria meningitidis; C484699:factor H-binding protein, Neisseria meningitidis