Safety and Immunogenicity of a Booster Dose of Meningococcal (Groups A, C, W, and Y) Polysaccharide Diphtheria Toxoid Conjugate Vaccine

Vaccine. 2016 Oct 17;34(44):5273-5278. doi: 10.1016/j.vaccine.2016.09.003. Epub 2016 Sep 15.

Abstract

Background: Quadrivalent meningococcal conjugate vaccines (MenACWY) were developed to offer long-term protection against invasive disease caused by serogroups A, C, W, and Y. Reduced MenACWY effectiveness within 5 years after primary vaccination (likely due to declining bactericidal antibody titers) has been described, particularly with respect to C and Y disease in the United States. We evaluated the safety and immunogenicity of a single booster dose of quadrivalent meningococcal polysaccharide diphtheria toxoid conjugate vaccine (MenACWY-D) in adolescents and adults who received a previous dose 4-6 years earlier.

Methods: This phase 2, open-label, multicenter study of 834 persons was conducted in the United States. Participants received a single 0.5-mL booster dose of MenACWY-D. Serogroup-specific bactericidal antibody geometric mean titers (GMTs) were measured with a serum bactericidal antibody assay using human complement (hSBA). Proportions of participants achieving antibody titers of ⩾1:8 for each vaccine serogroup on Days 6 and 28 were determined. Rates of adverse events (AEs), including serious adverse events (SAEs), were also assessed.

Results: Before booster vaccination, 38.7-68.5% of participants had an hSBA titer ⩾1:8, depending on vaccine serogroup. By Day 6 post-vaccination, 98.2-99.1% of participants had hSBA titers ⩾1:8. By Day 28, >99% of participants achieved this threshold and the primary hypothesis (lower limit of the one-sided 95% confidence limit ⩾85% for each serogroup) was met. The GMT ratios (post-vaccination divided by pre-vaccination) at Day 28 ranged from 47.2 (serogroup A) to 209.1 (serogroup Y). Rates of AEs, including SAEs, were similar to those observed among adolescents and adults who received a primary dose of MenACWY-D in previous studies. There were no study discontinuations due to an AE and no deaths.

Conclusions: Booster vaccination with MenACWY-D was safe and induced robust bactericidal antibody responses, consistent with immune memory, among adolescents and adults 4-6 years after primary vaccination. ClinicalTrials.gov registration: NCT01442675.

Keywords: Adolescent; Adult; Booster; Conjugate; Immunization; Meningococcal vaccines; Vaccines.

Publication types

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

MeSH terms

  • Adolescent
  • Adult
  • Adverse Drug Reaction Reporting Systems
  • Antibodies, Bacterial / blood
  • Diphtheria Toxoid / immunology*
  • Female
  • Humans
  • Immunization, Secondary*
  • Immunologic Memory
  • Male
  • Meningococcal Infections / immunology
  • Meningococcal Infections / prevention & control*
  • Meningococcal Vaccines / administration & dosage
  • Meningococcal Vaccines / adverse effects*
  • Meningococcal Vaccines / immunology*
  • Middle Aged
  • Neisseria meningitidis / classification
  • Neisseria meningitidis / immunology
  • Polysaccharides, Bacterial / immunology*
  • Serogroup
  • Serum Bactericidal Antibody Assay
  • Time Factors
  • United States
  • Vaccines, Conjugate / adverse effects
  • Vaccines, Conjugate / immunology
  • Young Adult

Substances

  • Antibodies, Bacterial
  • Diphtheria Toxoid
  • MenACWY-D vaccine
  • Meningococcal Vaccines
  • Polysaccharides, Bacterial
  • Vaccines, Conjugate

Associated data

  • ClinicalTrials.gov/NCT01442675