title: A bivalent Neisseria meningitidis recombinant lipidated factor H binding protein vaccine in young adults: results of a randomised, controlled, dose-escalation phase 1 trial.
abstract: Neisseria meningitidis is a leading cause of meningitis and septicaemia, but a broadly-protective vaccine against endemic serogroup B disease is not licensed and available. The conserved, outer-membrane lipoprotein factor H binding protein (fHBP, also known as LP2086) is expressed as one of two subfamily variants in virtually all meningococci. This study investigated the safety, tolerability, and immunogenicity of a recombinant-expressed bivalent fHBP (r-fHBP) vaccine in healthy adults. Participants (N=103) aged 18-25 years were recruited into three ascending dose level cohorts of 20, 60, and 200μg of a bivalent r-fHBP vaccine formulation and randomised to receive vaccine or placebo at 0, 1, and 6 months. The vaccine was well tolerated. Geometric mean titres (GMTs) for r-fHBP subfamily-specific IgG antibodies increased 19-168-fold from pre-vaccination to post-dose 2 in a dose level-dependent manner. In addition, robust serum bactericidal assay using human complement (hSBA) responses for strains expressing both homologous and heterologous fHBP variants were observed. After three vaccinations, 16-52% of the placebo group and 47-90%, 75-100%, and 88-100%, of the 20, 60, and 200μg dose levels, respectively, had seroprotective (≥ 1:4) hSBA titres against six serogroup B strains. The bivalent r-fHBP vaccine was well tolerated and induced robust bactericidal activity against six diverse serogroup B strains in young adults at the 60 and 200μg dose levels.
authors.affiliation: University of Western Australia School of Paediatrics and Child Health, Princess Margaret Hospital for Children and Vaccine Trials Group, Telethon Institute for Child Health Research, Perth, WA 6840, Australia. peter.richmond@uwa.edu.au
authors.forename: P C
authors.initials: PC
authors.lastname: Richmond
authors.forename: M D
authors.initials: MD
authors.lastname: Nissen
authors.forename: H S
authors.initials: HS
authors.lastname: Marshall
authors.forename: S B
authors.initials: SB
authors.lastname: Lambert
authors.forename: D
authors.initials: D
authors.lastname: Roberton
authors.forename: W C
authors.initials: WC
authors.lastname: Gruber
authors.forename: T R
authors.initials: TR
authors.lastname: Jones
authors.forename: A
authors.initials: A
authors.lastname: Arora
mesh_terms: D000328:Adult; D000907:Antibodies, Bacterial / Q000097:blood; D000942:Antigens, Bacterial / Q000276:immunology*; D001426:Bacterial Proteins / Q000276:immunology*; D003165:Complement System Proteins / Q000276:immunology; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D008297:Male; D008589:Meningococcal Infections / Q000517:prevention & control*; D022401:Meningococcal Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*; D038541:Neisseria meningitidis, Serogroup B / Q000276:immunology; D058248:Serum Bactericidal Antibody Assay; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D055815:Young Adult
chemical_list: D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D007074:Immunoglobulin G; D022401:Meningococcal Vaccines; D014614:Vaccines, Synthetic; C484699:factor H-binding protein, Neisseria meningitidis; D003165:Complement System Proteins