A Randomized, Controlled, Phase 1/2 Trial of a Neisseria Meningitidis Serogroup B Bivalent rLP2086 Vaccine in Healthy Children and Adolescents

Pediatr Infect Dis J. 2013 Apr;32(4):364-71. doi: 10.1097/INF.0b013e31827b0d24.

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.

Publication types

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

MeSH terms

  • Adolescent
  • Antigens, Bacterial / genetics
  • Antigens, Bacterial / immunology*
  • Australia
  • Bacterial Proteins / genetics
  • Bacterial Proteins / immunology*
  • Blood Bactericidal Activity
  • Child
  • Drug-Related Side Effects and Adverse Reactions / epidemiology
  • Drug-Related Side Effects and Adverse Reactions / pathology
  • Female
  • Humans
  • Male
  • Meningococcal Infections / immunology
  • Meningococcal Infections / prevention & control*
  • Meningococcal Vaccines / administration & dosage
  • Meningococcal Vaccines / adverse effects
  • Meningococcal Vaccines / genetics
  • Meningococcal Vaccines / immunology*
  • Neisseria meningitidis, Serogroup B / genetics
  • Neisseria meningitidis, Serogroup B / immunology*
  • Recombinant Proteins / genetics
  • Recombinant Proteins / immunology
  • Single-Blind Method
  • Vaccines, Synthetic / administration & dosage
  • Vaccines, Synthetic / adverse effects
  • Vaccines, Synthetic / genetics
  • Vaccines, Synthetic / immunology

Substances

  • Antigens, Bacterial
  • Bacterial Proteins
  • Meningococcal Vaccines
  • Recombinant Proteins
  • Vaccines, Synthetic
  • factor H-binding protein, Neisseria meningitidis