title: Randomized Trial to Compare the Immunogenicity and Safety of a CRM or TT Conjugated Quadrivalent Meningococcal Vaccine in Teenagers who Received a CRM or TT Conjugated Serogroup C Vaccine at Preschool Age.
abstract: BACKGROUND
  Protection after meningococcal C (MenC) conjugate (MCC) vaccination in early childhood is short-lived. Boosting with a quadrivalent vaccine in teenage years, a high-risk period for MenC disease, should protect against additional serogroups but might compromise MenC response. The carrier protein in the primary MCC vaccine determines the response to MCC booster in toddlers, but the relationship between primary vaccine and booster given later is unclear. This study compared responses to a CRM-conjugated or tetanus toxoid (TT)-conjugated MenACWY vaccine in teenagers primed with different MCC vaccines at preschool age.
  
  
  METHODS
  Ninety-three teenagers (16-19 years), who were previously randomized at age 3-6 years to receive single-dose MCC-CRM or MCC-TT, were randomized to receive either MenACWY-CRM or MenACWY-TT booster. Serum bactericidal antibodies (SBA, protective titer ≥ 8) were measured before, 1 month and 6 or 9 months after boosting.
  
  
  RESULTS
  Preboosting, MCC-TT-primed teenagers had significantly higher MenC SBA titers than those MCC-CRM-primed (P = 0.02). Postboosting, both MenACWY vaccines induced protective SBA titers to all 4 serogroups in most participants (≥ 98% at 1 month and ≥ 90% by 9 months postboost). The highest MenC SBA titers were seen in those MCC-TT-primed and MenACWY-TT-boosted [geometric mean titer (GMT) ~ 22,000] followed by those boosted with MenACWY-CRM irrespective of priming (GMT ~ 12,000) and then those MCC-CRM-primed and MenACWY-TT-boosted (GMT ~ 5500). The estimated postbooster MenC SBA decline beyond 1 month was ~40% as time since booster doubles. Both vaccines were well tolerated with no attributable serious adverse events.
  
  
  CONCLUSIONS
  Both MenACWY vaccines safely induced protective sustained antibody responses against all targeted serogroups in MCC-primed teenagers.
authors.affiliation: From the *Department of Immunisation, Hepatitis and Blood Transfusion, Public Health England (PHE), London, United Kingdom; †Department of Infection and Population Health, University College London, London, United Kingdom; ‡Statistics, Modelling, and Economics Department, PHE London, United Kingdom; §Department of Clinical Epidemiology, Communicable Disease Centre, Tan Tock Seng Hospital, Singapore; ¶Vaccine Evaluation Unit, PHE, Manchester Medical Microbiology Partnership, Manchester Royal Infirmary, Manchester, United Kingdom; and ‖ Microbiology Services, PHE, Porton Down, Salisbury, United Kingdom.
authors.forename: David A
authors.initials: DA
authors.lastname: Ishola
authors.forename: Nick
authors.initials: N
authors.lastname: Andrews
authors.forename: Pauline
authors.initials: P
authors.lastname: Waight
authors.forename: Chee-Fu
authors.initials: CF
authors.lastname: Yung
authors.forename: Jo
authors.initials: J
authors.lastname: Southern
authors.forename: Xilian
authors.initials: X
authors.lastname: Bai
authors.forename: Helen
authors.initials: H
authors.lastname: Findlow
authors.forename: Mary
authors.initials: M
authors.lastname: Matheson
authors.forename: Anna
authors.initials: A
authors.lastname: England
authors.forename: Bassam
authors.initials: B
authors.lastname: Hallis
authors.forename: Jamie
authors.initials: J
authors.lastname: Findlow
authors.forename: Ray
authors.initials: R
authors.lastname: Borrow
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Miller
mesh_terms: D000293:Adolescent; D000328:Adult; D000907:Antibodies, Bacterial / Q000097:blood* / Q000276:immunology; D006801:Humans; D007117:Immunization, Secondary; D022401:Meningococcal Vaccines / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology*; D009345:Neisseria meningitidis / Q000276:immunology*; D018074:Vaccines, Conjugate / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D055815:Young Adult
chemical_list: D000907:Antibodies, Bacterial; D022401:Meningococcal Vaccines; D018074:Vaccines, Conjugate