title: A Phase 2, Randomized, Active-controlled, Observer-blinded Study to Assess the Immunogenicity, Tolerability and Safety of Bivalent rLP2086, a Meningococcal Serogroup B Vaccine, Coadministered With Tetanus, Diphtheria and Acellular Pertussis Vaccine and Serogroup A, C, Y and W-135 Meningococcal Conjugate Vaccine in Healthy US Adolescents.
abstract: Bivalent rLP2086, targeting meningococcal serogroup B, will extend prevention of meningococcal disease beyond that provided by quadrivalent serogroup ACWY vaccines; coadministration with recommended vaccines may improve adherence to vaccine schedules. This phase 2, randomized, active-controlled, observer-blinded study assessed whether immune responses induced by coadministration of Menactra (meningococcal A, C, Y and W-135 polysaccharide conjugate vaccine [MCV4]) and Adacel (tetanus toxoid, reduced diphtheria toxoid, acellular pertussis vaccine [Tdap]) with bivalent rLP2086 (Trumenba [meningococcal serogroup B vaccine], approved in the United States) were noninferior to MCV4 + Tdap or bivalent rLP2086 alone.
  
  
  
  Healthy adolescents aged 10 to <13 years received MCV4 + Tdap + bivalent rLP2086, MCV4 + Tdap or bivalent rLP2086. Bivalent rLP2086 response was assessed with serum bactericidal assays using human complement with 2 meningococcal serogroup B test strains expressing vaccine-heterologous factor H-binding protein variants; MCV4 with SBAs using rabbit complement; and Tdap with multiplexed Luminex assays. Safety was evaluated.
  
  
  
  Two thousand six hundred forty-eight subjects were randomized. Immune responses to MCV4 + Tdap + bivalent rLP2086 were noninferior to MCV4 + Tdap or bivalent rLP2086 alone. Seroprotective serum bactericidal assays using human complement titers were documented for 62.3%-68.0% and 87.5%-90% of MCV4 + Tdap + bivalent rLP2086 recipients after doses 2 and 3, respectively. A ≥4-fold rise in serum bactericidal assays using human complement titers from baseline was achieved by 56.3%-64.3% and 84.0%-85.7% of subjects after doses 2 and 3, respectively. Bivalent rLP2086 alone induced similar responses. Concomitant administration did not substantially increase reactogenicity compared with bivalent rLP2086 alone.
  
  
  
  Bivalent rLP2086 given concomitantly with MCV4 + Tdap met all noninferiority immunogenicity criteria without a clinically meaningful increase in reactogenicity. MCV4 and bivalent rLP2086 coadministration would provide coverage against the 5 major disease-causing serogroups.
authors.affiliation: From the *Jean Brown Research and †Foothill Family Clinic, Salt Lake City, UT; ‡Pfizer Vaccine Clinical Research, Collegeville, PA; §Pfizer Vaccine Clinical Research, ¶Pfizer Vaccine Research Operations and Strategy, and ‖Pfizer Vaccine Research and Development, Pearl River, NY; and **Pfizer Medical and Scientific Affairs, Collegeville, PA.
authors.forename: Derek
authors.initials: D
authors.lastname: Muse
authors.forename: Shane
authors.initials: S
authors.lastname: Christensen
authors.forename: Prakash
authors.initials: P
authors.lastname: Bhuyan
authors.forename: Judith
authors.initials: J
authors.lastname: Absalon
authors.forename: Joseph J
authors.initials: JJ
authors.lastname: Eiden
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Jones
authors.forename: Laura J
authors.initials: LJ
authors.lastname: York
authors.forename: Kathrin U
authors.initials: KU
authors.lastname: Jansen
authors.forename: Robert E
authors.initials: RE
authors.lastname: O'Neill
authors.forename: Shannon L
authors.initials: SL
authors.lastname: Harris
authors.forename: John L
authors.initials: JL
authors.lastname: Perez
mesh_terms: D000907:Antibodies, Bacterial / Q000097:blood*; D000942:Antigens, Bacterial / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology*; D001426:Bacterial Proteins / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology*; D001770:Blood Bactericidal Activity; D002648:Child; D022681:Diphtheria-Tetanus-acellular Pertussis Vaccines / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology*; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D008297:Male; D022401:Meningococcal Vaccines / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology*; D016037:Single-Blind Method; D016896:Treatment Outcome; D014481:United States
chemical_list: D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D022681:Diphtheria-Tetanus-acellular Pertussis Vaccines; D022401:Meningococcal Vaccines; C509326:adacel; C484699:factor H-binding protein, Neisseria meningitidis