Immunogenicity and Safety of Investigational Vaccine Formulations Against Meningococcal Serogroups A, B, C, W, and Y in Healthy Adolescents

Hum Vaccin Immunother. 2015;11(6):1507-17. doi: 10.1080/21645515.2015.1029686.

Abstract

This phase 2 study assessed the immunogenicity, safety, and reactogenicity of investigational formulations of meningococcal ABCWY vaccines, consisting of recombinant proteins (rMenB) and outer membrane vesicle (OMV) components of a licensed serogroup B vaccine, combined with components of a licensed quadrivalent meningococcal glycoconjugate vaccine (MenACWY-CRM). A total of 495 healthy adolescents were randomized to 6 groups to receive 2 doses (Months 0, 2) of one of 4 formulations of rMenB antigens, with or without OMV, combined with MenACWY-CRM, or 2 doses of rMenB alone or one dose of MenACWY-CRM then a placebo. Immunogenicity was assessed by serum bactericidal assay with human complement (hSBA) against serogroups ACWY and serogroup B test strains; solicited reactions and any adverse events (AEs) were assessed. Two MenABCWY vaccinations elicited robust ACWY immune responses, with higher seroresponse rates than one dose of MenACWY-CRM. Bactericidal antibody responses against the rMenB antigens and OMV components were highest in subjects who received 2 doses of OMV-containing MenABCWY formulations, with ≥68% of subjects achieving hSBA titers ≥5 against each of the serogroup B test strains. After the first dose, solicited local reaction rates were higher in the MenABCWY or rMenB groups than the MenACWY-CRM group, but similar across groups after the second dose, consisting mainly of transient injection site pain. Fever (≥38.0°C) was rare and there were no vaccine-related serious AEs. In conclusion, investigational MenABCWY formulations containing OMV components elicited highly immunogenic responses against meningococcal serogroups ACWY, as well as serogroup B test strains, with an acceptable safety profile. [NCT01210885].

Keywords: AE, adverse event; CI, confidence interval; GMT, geometric mean titer; IMD, invasive meningococcal disease; NHBA, Neisserial Heparin Binding Antigen; NadA, Neisseria adhesin A; Neisseria meningitidis; OMV, outer membrane vesicle; PP, per-protocol set; SAE, serious adverse event; adolescents; conjugate vaccine; fHbp, factor H-binding protein; hSBA, serum bactericidal assay with human complement; immunogenicity; meningococcal disease; safety.

Publication types

  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Blood Bactericidal Activity
  • Drug-Related Side Effects and Adverse Reactions / epidemiology
  • Drug-Related Side Effects and Adverse Reactions / pathology
  • Drugs, Investigational / administration & dosage
  • Drugs, Investigational / adverse effects*
  • Female
  • Healthy Volunteers
  • Humans
  • Male
  • Meningococcal Vaccines / administration & dosage
  • Meningococcal Vaccines / adverse effects*
  • Meningococcal Vaccines / immunology*
  • Placebos / administration & dosage
  • Vaccines, Combined / administration & dosage
  • Vaccines, Combined / adverse effects
  • Vaccines, Combined / immunology

Substances

  • Drugs, Investigational
  • Meningococcal Vaccines
  • Placebos
  • Vaccines, Combined

Associated data

  • ClinicalTrials.gov/NCT01210885