Multicenter, open-label, randomized phase II controlled trial of an investigational recombinant Meningococcal serogroup B vaccine with and without outer membrane vesicles, administered in infancy

Clin Infect Dis. 2010 Nov 15;51(10):1127-37. doi: 10.1086/656741. Epub 2010 Oct 18.

Abstract

Background: In the absence of an efficacious broadly protective vaccine, serogroup B Neisseria meningitidis (MenB) is the leading cause of bacterial meningitis and septicemia in many industrialized countries. An investigational recombinant vaccine that contains 3 central proteins; Neisserial adhesin A (NadA), factor H binding protein (fHBP) and Neisserial heparin binding antigen (NHBA) has been developed. These antigens have been formulated with and without outer membrane vesicles (rMenB+OMV and rMenB, respectively) from the New Zealand epidemic strain (B:4:P1.7-2,4). In this trial, we assessed the immunogenicity of these formulations in infants, who are at greatest risk of contracting MenB disease.

Methods: A total of 147 infants from the United Kingdom were enrolled and randomly assigned to receive rMenB or rMenB+OMV at 2, 4, 6, and 12 months of age or a single dose at 12 months of age. Serum samples taken before and after vaccination were assayed in a standardized serum bactericidal antibody assay against 7 MenB strains. Local and systemic reactogenicity were recorded for 7 days after each vaccination. Analysis was according to protocol.

Results: After 3 doses, both vaccines were immunogenic against strains expressing homologous or related NadA and fHBP. rMenB+OMV demonstrated greater immunogenicity than did rMenB and was immunogenic against strains expressing homologous PorA. Both vaccines elicited anamnestic responses after the fourth dose. For both vaccines, responses were lower against strains expressing heterologous fHBP variants and after a single dose at 12 months.

Conclusions: The rMenB+OMV vaccine has the potential to protect infants from MenB disease, although the breadth of protection afforded to heterologous antigens requires additional investigation.

Publication types

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

MeSH terms

  • Adhesins, Bacterial / genetics
  • Adhesins, Bacterial / immunology
  • Antibodies, Bacterial / blood
  • Antigens, Bacterial / immunology
  • Bacterial Outer Membrane Proteins / genetics
  • Bacterial Outer Membrane Proteins / immunology*
  • Cell Membrane / immunology
  • Drug-Related Side Effects and Adverse Reactions
  • Female
  • Humans
  • Immunization Schedule
  • Infant
  • Male
  • Meningitis, Meningococcal / immunology
  • Meningitis, Meningococcal / prevention & control*
  • Meningococcal Vaccines / administration & dosage*
  • Meningococcal Vaccines / adverse effects
  • Meningococcal Vaccines / immunology
  • Neisseria meningitidis, Serogroup B / chemistry
  • Neisseria meningitidis, Serogroup B / genetics
  • Neisseria meningitidis, Serogroup B / immunology*
  • Serum Bactericidal Antibody Assay
  • United Kingdom
  • Vaccines, Synthetic / administration & dosage
  • Vaccines, Synthetic / adverse effects
  • Vaccines, Synthetic / immunology

Substances

  • Adhesins, Bacterial
  • Antibodies, Bacterial
  • Antigens, Bacterial
  • Bacterial Outer Membrane Proteins
  • Meningococcal Vaccines
  • NadA protein, Neisseria meningitidis
  • Vaccines, Synthetic