title: Immunogenicity of reduced dose priming schedules of serogroup C meningococcal conjugate vaccine followed by booster at 12 months in infants: open label randomised controlled trial.
abstract: OBJECTIVE
  To determine whether the immunogenicity of a single dose infant priming schedule of serogroup C meningococcal (MenC) conjugate vaccine is non-inferior to a two dose priming schedule when followed by a booster dose at age 12 months.
  
  
  METHODS
  Phase IV open label randomised controlled trial carried out from July 2010 until August 2013 SETTING: Four centres in the United Kingdom and one centre in Malta.
  
  
  METHODS
  Healthy infants aged 6-12 weeks followed up until age 24 months.
  
  
  METHODS
  In the priming phase of the trial 509 infants were randomised in a 10:10:7:4 ratio into four groups to receive either a single MenC-cross reacting material 197 (CRM) dose at 3 months; two doses of MenC-CRM at 3 and 4 months; a single MenC-polysaccharide-tetanus toxoid (TT) dose at 3 months; or no MenC doses, respectively. Haemophilus influenzae type b (Hib)-MenC-TT vaccine was administered to all infants at 12 months of age. All infants also received the nationally routinely recommended vaccines. Blood samples were taken at age 5, 12, 13, and 24 months.
  
  
  METHODS
  MenC serum bactericidal antibody assay with rabbit complement (rSBA) one month after the Hib-MenC-TT vaccine. Non-inferiority was met if the lower 95% confidence limit of the difference in the mean log10 MenC rSBA between the single dose MenC-CRM and the two dose MenC-CRM groups was >-0.35.
  
  
  RESULTS
  The primary objective was met: after a Hib-MenC-TT booster dose at 12 months of age the MenC rSBA geometric mean titres induced in infants primed with a single MenC-CRM dose were not inferior to those induced in participants primed with two MenC-CRM doses in infancy (660 (95% confidence interval 498 to 876) v 295 (220 to 398)) with a corresponding difference in the mean log10 MenC rSBA of 0.35 (0.17 to 0.53) that showed superiority of the single over the two dose schedule). Exploration of differences between the priming schedules showed that one month after Hib-MenC-TT vaccination, MenC rSBA ≥ 1:8 was observed in >96% of participants previously primed with any of the MenC vaccine schedules in infancy and in 83% of those who were not vaccinated against MenC in infancy. The MenC rSBA geometric mean titres induced by the Hib-MenC-TT boost were significantly higher in children who were primed with one rather than two MenC-CRM doses in infancy. Only priming with MenC-TT, however, induced robust MenC bactericidal antibody after the Hib-MenC-TT booster that persisted until 24 months of age.
  
  
  CONCLUSIONS
  MenC vaccination programmes with two MenC infant priming doses could be reduced to a single priming dose without reducing post-boost antibody titres. When followed by a Hib-MenC-TT booster dose, infant priming with a single MenC-TT vaccine dose induces a more robust antibody response than one or two infant doses of MenC-CRM. Bactericidal antibody induced by a single Hib-MenC-TT conjugate vaccine dose at 12 months of age (that is, a toddler only schedule), without infant priming, is not well sustained at 24 months. Because of rapid waning of MenC antibody, programmes using toddler only schedules will still need to rely on herd protection to protect infants and young children.Trial registration Eudract No: 2009-016579-31; NCT01129518; study ID: 2008_06 (http://clinicaltrials.gov).
authors.affiliation: Malta Children's Vaccine Group, Mater Dei Hospital, Tal-Qroqq, Msida, MSD 2090, Malta dpace@go.net.mt.
authors.forename: David
authors.initials: D
authors.lastname: Pace
authors.affiliation: Oxford Vaccine Group, Department of Paediatrics, University of Oxford and the NIHR Oxford Biomedical Research Centre, Oxford, UK.
authors.forename: Ameneh
authors.initials: A
authors.lastname: Khatami
authors.affiliation: Oxford Vaccine Group, Department of Paediatrics, University of Oxford and the NIHR Oxford Biomedical Research Centre, Oxford, UK.
authors.forename: Jennifer
authors.initials: J
authors.lastname: McKenna
authors.affiliation: Oxford Vaccine Group, Department of Paediatrics, University of Oxford and the NIHR Oxford Biomedical Research Centre, Oxford, UK.
authors.forename: Danielle
authors.initials: D
authors.lastname: Campbell
authors.affiliation: Malta Children's Vaccine Group, Mater Dei Hospital, Tal-Qroqq, Msida, MSD 2090, Malta.
authors.forename: Simon
authors.initials: S
authors.lastname: Attard-Montalto
authors.affiliation: Centre for Statistics in Medicine, NIHR Oxford Biomedical Research Centre, University of Oxford, Oxford, UK.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Birks
authors.affiliation: Primary Care Clinical Trials Unit, Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK.
authors.forename: Merryn
authors.initials: M
authors.lastname: Voysey
authors.affiliation: Bristol Children's Vaccine Centre, University Hospitals Bristol NHS Foundation Trust and University of Bristol, Bristol, UK.
authors.forename: Catherine
authors.initials: C
authors.lastname: White
authors.affiliation: Bristol Children's Vaccine Centre, University Hospitals Bristol NHS Foundation Trust and University of Bristol, Bristol, UK.
authors.forename: Adam
authors.initials: A
authors.lastname: Finn
authors.affiliation: Southampton NIHR Wellcome Trust Clinical Research Facility, University Hospital Southampton NHS Foundation Trust, Southampton, UK.
authors.forename: Emma
authors.initials: E
authors.lastname: Macloed
authors.affiliation: Southampton NIHR Wellcome Trust Clinical Research Facility, University Hospital Southampton NHS Foundation Trust, Southampton, UK Academic Unit of Clinical and Experimental Sciences, Faculty of Medicine and Institute for Life Sciences, University of Southampton, Southampton, UK.
authors.forename: Saul N
authors.initials: SN
authors.lastname: Faust
authors.affiliation: St George's Vaccine Institute, St George's University of London, London, UK.
authors.forename: Alison Louise
authors.initials: AL
authors.lastname: Kent
authors.affiliation: St George's Vaccine Institute, St George's University of London, London, UK.
authors.forename: Paul T
authors.initials: PT
authors.lastname: Heath
authors.affiliation: Vaccine Evaluation Unit, Public Health England, Public Health Laboratory Manchester, Manchester Royal Infirmary, Manchester, UK.
authors.forename: Ray
authors.initials: R
authors.lastname: Borrow
authors.affiliation: Oxford Vaccine Group, Department of Paediatrics, University of Oxford and the NIHR Oxford Biomedical Research Centre, Oxford, UK.
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Snape
authors.affiliation: Oxford Vaccine Group, Department of Paediatrics, University of Oxford and the NIHR Oxford Biomedical Research Centre, Oxford, UK.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Pollard
mesh_terms: D002675:Child, Preschool; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007115:Immunization Schedule; D007117:Immunization, Secondary; D007223:Infant; D008297:Male; D008319:Malta; D022401:Meningococcal Vaccines / Q000276:immunology*; D015233:Models, Statistical; D058248:Serum Bactericidal Antibody Assay; D006113:United Kingdom; D018074:Vaccines, Conjugate / Q000276:immunology
chemical_list: D022401:Meningococcal Vaccines; D018074:Vaccines, Conjugate; C410218:serogroup C meningococcal conjugate vaccine
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