A Bivalent Neisseria Meningitidis Recombinant Lipidated Factor H Binding Protein Vaccine in Young Adults: Results of a Randomised, Controlled, Dose-Escalation Phase 1 Trial

Vaccine. 2012 Sep 21;30(43):6163-74. doi: 10.1016/j.vaccine.2012.07.065. Epub 2012 Aug 5.

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.

Publication types

  • Clinical Trial, Phase I
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antibodies, Bacterial / blood
  • Antigens, Bacterial / immunology*
  • Bacterial Proteins / immunology*
  • Complement System Proteins / immunology
  • Double-Blind Method
  • Female
  • Humans
  • Immunoglobulin G / blood
  • Male
  • Meningococcal Infections / prevention & control*
  • Meningococcal Vaccines / administration & dosage
  • Meningococcal Vaccines / adverse effects
  • Meningococcal Vaccines / immunology*
  • Neisseria meningitidis, Serogroup B / immunology
  • Serum Bactericidal Antibody Assay
  • Vaccines, Synthetic / administration & dosage
  • Vaccines, Synthetic / adverse effects
  • Vaccines, Synthetic / immunology
  • Young Adult

Substances

  • Antibodies, Bacterial
  • Antigens, Bacterial
  • Bacterial Proteins
  • Immunoglobulin G
  • Meningococcal Vaccines
  • Vaccines, Synthetic
  • factor H-binding protein, Neisseria meningitidis
  • Complement System Proteins