title: Safety and immunogenicity of a booster dose of meningococcal (groups A, C, W, and Y) polysaccharide diphtheria toxoid conjugate vaccine.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Scientific and Medical Affairs Department, Sanofi Pasteur Inc., Discovery Drive, Swiftwater, PA 18370, USA. Electronic address: corey.robertson@sanofipasteur.com.
authors.forename: Corwin A
authors.initials: CA
authors.lastname: Robertson
authors.affiliation: Scientific and Medical Affairs Department, Sanofi Pasteur Inc., Discovery Drive, Swiftwater, PA 18370, USA; Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA. Electronic address: greenbed@pitt.edu.
authors.forename: David P
authors.initials: DP
authors.lastname: Greenberg
authors.affiliation: Kentucky Pediatric/Adult Research, 201 South 5th Street, Bardstown, KY 40004, USA. Electronic address: jhedrick@bardstowncable.net.
authors.forename: James
authors.initials: J
authors.lastname: Hedrick
authors.affiliation: Legacy Pediatrics, 1815 South Clinton Avenue, Suite 360, Rochester, NY 14618, USA. Electronic address: michael.pichichero@rochesterregional.org.
authors.forename: Michael
authors.initials: M
authors.lastname: Pichichero
authors.affiliation: Scientific and Medical Affairs Department, Sanofi Pasteur Inc., Discovery Drive, Swiftwater, PA 18370, USA; Department of Health Policy, Vanderbilt University School of Medicine, Nashville, TN 37212, USA. Electronic address: michael.decker@vanderbilt.edu.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Decker
authors.affiliation: Huguenot Pediatrics, 1407 Huguenot Road, Midlothian, VA 23113, USA. Electronic address: mks8400@comcast.net.
authors.forename: Martha
authors.initials: M
authors.lastname: Saunders
mesh_terms: D000293:Adolescent; D000328:Adult; D016907:Adverse Drug Reaction Reporting Systems; D000907:Antibodies, Bacterial / Q000097:blood; D004168:Diphtheria Toxoid / Q000276:immunology*; D005260:Female; D006801:Humans; D007117:Immunization, Secondary; D007156:Immunologic Memory; D008297:Male; D008589:Meningococcal Infections / Q000276:immunology / Q000517:prevention & control*; D022401:Meningococcal Vaccines / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology*; D008875:Middle Aged; D009345:Neisseria meningitidis / Q000145:classification / Q000276:immunology; D011135:Polysaccharides, Bacterial / Q000276:immunology*; D065288:Serogroup; D058248:Serum Bactericidal Antibody Assay; D013997:Time Factors; D014481:United States; D018074:Vaccines, Conjugate / Q000009:adverse effects / Q000276:immunology; D055815:Young Adult
chemical_list: D000907:Antibodies, Bacterial; D004168:Diphtheria Toxoid; C568160:MenACWY-D vaccine; D022401:Meningococcal Vaccines; D011135:Polysaccharides, Bacterial; D018074:Vaccines, Conjugate
keywords: Adolescent; Adult; Booster; Conjugate; Immunization; Meningococcal vaccines; Vaccines