title: Bactericidal activity of sera from adolescents vaccinated with bivalent rLP2086 against meningococcal serogroup B outbreak strains from France.
abstract: Bivalent rLP2086 (Trumenba®; MenB-FHbp), composed of two factor H binding proteins (FHbps), is a vaccine approved in the United States for prevention of Neisseria meningitidis serogroup B (MnB) invasive meningococcal disease (IMD). Bactericidal activity of sera from subjects vaccinated with bivalent rLP2086 was assessed against MnB isolates from recent disease outbreaks in France.
  
  
  
  MnB isolates from IMD cases were characterized by whole genome sequencing and FHbp expression was assessed using a flow cytometry-based assay. Sera from subjects (11-<19years old) vaccinated with bivalent rLP2086 at 0, 2, and 6months were evaluated. Bactericidal activity was measured in serum bactericidal assays using human complement (hSBAs). The response rate (RR) represents the percentage of subjects with an hSBA titer ⩾1:4.
  
  
  
  The six MnB outbreak isolates expressed diverse FHbp variants: A22, B03, B24 (two isolates), B44, and B228. FHbp expression levels ranged from 1309 to 8305 (mean fluorescence intensity units). The RR of preimmune sera from subjects was 7% to 27%. RRs increased for all isolates after each vaccine dose. After two doses, RRs ranged from 40% to 93%. After dose 3, RRs were ⩾73% for all isolates (range, 73%-100%).
  
  
  
  Each of the representative French outbreak isolates was killed by sera from subjects vaccinated with bivalent rLP2086. Vaccination elicited an immune response with bactericidal activity against these diverse isolates in a large proportion of subjects at risk. These results provide additional support for the licensure strategy of testing MnB strains expressing vaccine-heterologous FHbp variants in hSBAs and further illustrate the breadth of efficacy of this protein-based MnB vaccine.
authors.affiliation: Institut Pasteur, Invasive Bacterial Infections Unit, 25-28 Rue du Docteur Roux, 75015 Paris, France.
authors.forename: Muhamed-Kheir
authors.initials: MK
authors.lastname: Taha
authors.affiliation: Pfizer Vaccine Research and Development, 401 N Middletown Rd, Pearl River, NY 10965, USA.
authors.forename: Julio Cesar
authors.initials: JC
authors.lastname: Hawkins
authors.affiliation: Pfizer Vaccine Research and Development, 401 N Middletown Rd, Pearl River, NY 10965, USA.
authors.forename: Paul
authors.initials: P
authors.lastname: Liberator
authors.affiliation: Institut Pasteur, Invasive Bacterial Infections Unit, 25-28 Rue du Docteur Roux, 75015 Paris, France.
authors.forename: Ala-Eddine
authors.initials: AE
authors.lastname: Deghmane
authors.affiliation: Pfizer Vaccine Research and Development, 401 N Middletown Rd, Pearl River, NY 10965, USA.
authors.forename: Lubomira
authors.initials: L
authors.lastname: Andrew
authors.affiliation: Pfizer Vaccine Research and Development, 401 N Middletown Rd, Pearl River, NY 10965, USA.
authors.forename: Li
authors.initials: L
authors.lastname: Hao
authors.affiliation: Pfizer Vaccine Research and Development, 401 N Middletown Rd, Pearl River, NY 10965, USA.
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Jones
authors.affiliation: Pfizer Vaccine Research and Development, 401 N Middletown Rd, Pearl River, NY 10965, USA.
authors.forename: Lisa K
authors.initials: LK
authors.lastname: McNeil
authors.affiliation: Pfizer Vaccine Research and Development, 401 N Middletown Rd, Pearl River, NY 10965, USA.
authors.forename: Robert E
authors.initials: RE
authors.lastname: O'Neill
authors.affiliation: Pfizer Vaccine Research, 500 Arcola Rd, Collegeville, PA 19426, USA.
authors.forename: John L
authors.initials: JL
authors.lastname: Perez
authors.affiliation: Pfizer Vaccine Research and Development, 401 N Middletown Rd, Pearl River, NY 10965, USA.
authors.forename: Kathrin U
authors.initials: KU
authors.lastname: Jansen
authors.affiliation: Pfizer Vaccine Research and Development, 401 N Middletown Rd, Pearl River, NY 10965, USA. Electronic address: annaliesa.anderson@pfizer.com.
authors.forename: Annaliesa S
authors.initials: AS
authors.lastname: Anderson
mesh_terms: D000293:Adolescent; D000942:Antigens, Bacterial / Q000032:analysis / Q000235:genetics / Q000276:immunology*; D001426:Bacterial Proteins / Q000032:analysis / Q000235:genetics / Q000276:immunology*; D001770:Blood Bactericidal Activity; D002648:Child; D003165:Complement System Proteins / Q000276:immunology; D004196:Disease Outbreaks; D005260:Female; D005602:France / Q000453:epidemiology; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D022401:Meningococcal Vaccines / Q000008:administration & dosage / Q000276:immunology*; D050296:Microbial Viability; D038541:Neisseria meningitidis, Serogroup B / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D022401:Meningococcal Vaccines; C484699:factor H-binding protein, Neisseria meningitidis; D003165:Complement System Proteins
keywords: Bivalent rLP2086; Factor H binding protein; Invasive meningococcal disease; MenB-FHbp; Neisseria meningitidis serogroup B; Outbreak