title: A randomized, controlled, phase 1/2 trial of a Neisseria meningitidis serogroup B bivalent rLP2086 vaccine in healthy children and adolescents.
abstract: BACKGROUND
  Neisseria meningitidis serogroup B (MnB) is a significant cause of invasive meningococcal disease. Factor H binding protein (also known as LP2086) is a conserved outer membrane neisserial lipoprotein that has emerged as a strong candidate protein antigen for MnB vaccination. This study examined the safety, tolerability and immunogenicity of an initial formulation of a bivalent recombinant LP2086 (rLP2086) vaccine in healthy children and adolescents.
  
  
  METHODS
  In this randomized, observer-blinded, parallel-group, multicenter trial conducted at 6 centers in Australia, 127 healthy participants aged 8-14 years were assigned to receive 20, 60 or 200 µg of the bivalent rLP2086 vaccine (n = 16, 45 and 45, respectively) or active control (Twinrix, n = 21) at 0, 1 and 6 months. Immunogenicity was assessed before the first dose and 1 month after doses 2 and 3. Local reactions, systemic events and other adverse events were recorded. The primary immunogenicity endpoint was the rate of seroconversion (≥4-fold rise in human complement serum bactericidal assay titer) against MnB strains expressing the homologous A05 or heterologous B02 LP2086 variants.
  
  
  RESULTS
  The bivalent rLP2086 vaccine was generally well-tolerated, with mostly mild to moderate local reactions. The most common adverse events, headache and upper respiratory tract infection, occurred with similar frequency in each group. Post-dose 3 seroconversion rates against strains expressing B02 and A05 variants were 68.8-95.3% for rLP2086 recipients and 0% for Twinrix recipients.
  
  
  CONCLUSIONS
  The bivalent rLP2086 vaccine was well-tolerated and immunogenic in healthy children and adolescents, supporting further evaluation as a broadly protective MnB vaccine.
authors.affiliation: Queensland Paediatric Infectious Diseases Laboratory, Queensland Children's Medical Research Institute, Royal Children's Hospital and University of Queensland, Herston, Queensland, Australia. theniss@uq.edu.au
authors.forename: Michael D
authors.initials: MD
authors.lastname: Nissen
authors.forename: Helen S
authors.initials: HS
authors.lastname: Marshall
authors.forename: Peter C
authors.initials: PC
authors.lastname: Richmond
authors.forename: Qin
authors.initials: Q
authors.lastname: Jiang
authors.forename: Shannon L
authors.initials: SL
authors.lastname: Harris
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Jones
authors.forename: Kathrin U
authors.initials: KU
authors.lastname: Jansen
authors.forename: John L
authors.initials: JL
authors.lastname: Perez
mesh_terms: D000293:Adolescent; D000942:Antigens, Bacterial / Q000235:genetics / Q000276:immunology*; D001315:Australia; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology*; D001770:Blood Bactericidal Activity; D002648:Child; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D008589:Meningococcal Infections / Q000276:immunology / Q000517:prevention & control*; D022401:Meningococcal Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000235:genetics / Q000276:immunology*; D038541:Neisseria meningitidis, Serogroup B / Q000235:genetics / Q000276:immunology*; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology; D016037:Single-Blind Method; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000009:adverse effects / Q000235:genetics / Q000276:immunology
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D022401:Meningococcal Vaccines; D011994:Recombinant Proteins; D014614:Vaccines, Synthetic; C484699:factor H-binding protein, Neisseria meningitidis