title: Effect of a quadrivalent meningococcal ACWY glycoconjugate or a serogroup B meningococcal vaccine on meningococcal carriage: an observer-blind, phase 3 randomised clinical trial.
abstract: BACKGROUND
  Meningococcal conjugate vaccines protect individuals directly, but can also confer herd protection by interrupting carriage transmission. We assessed the effects of meningococcal quadrivalent glycoconjugate (MenACWY-CRM) or serogroup B (4CMenB) vaccination on meningococcal carriage rates in 18-24-year-olds.
  
  
  METHODS
  In this phase 3, observer-blind, randomised controlled trial, university students aged 18-24 years from ten sites in England were randomly assigned (1:1:1, block size of three) to receive two doses 1 month apart of Japanese Encephalitis vaccine (controls), 4CMenB, or one dose of MenACWY-CRM then placebo. Participants were randomised with a validated computer-generated random allocation list. Participants and outcome-assessors were masked to the treatment group. Meningococci were isolated from oropharyngeal swabs collected before vaccination and at five scheduled intervals over 1 year. Primary outcomes were cross-sectional carriage 1 month after each vaccine course. Secondary outcomes included comparisons of carriage at any timepoint after primary analysis until study termination. Reactogenicity and adverse events were monitored throughout the study. Analysis was done on the modified intention-to-treat population, which included all enrolled participants who received a study vaccination and provided at least one assessable swab after baseline. This trial is registered with ClinicalTrials.gov, registration number NCT01214850.
  
  
  RESULTS
  Between Sept 21 and Dec 21, 2010, 2954 participants were randomly assigned (987 assigned to control [984 analysed], 979 assigned to 4CMenB [974 analysed], 988 assigned to MenACWY-CRM [983 analysed]); 33% of the 4CMenB group, 34% of the MenACWY-CRM group, and 31% of the control group were positive for meningococcal carriage at study entry. By 1 month, there was no significant difference in carriage between controls and 4CMenB (odds ratio 1·2, 95% CI 0·8-1·7) or MenACWY-CRM (0·9, [0·6-1·3]) groups. From 3 months after dose two, 4CMenB vaccination resulted in significantly lower carriage of any meningococcal strain (18·2% [95% CI 3·4-30·8] carriage reduction), capsular groups BCWY (26·6% [10·5-39·9] carriage reduction), capsular groups CWY (29·6% [8·1-46·0] carriage reduction), and serogroups CWY (28·5% [2·8-47·5] carriage reduction) compared with control vaccination. Significantly lower carriage rates were also noted in the MenACWY-CRM group compared with controls: 39·0% (95% CI 17·3-55·0) carriage reduction for serogroup Y and 36·2% (15·6-51·7) carriage reduction for serogroup CWY. Study vaccines were generally well tolerated, with increased rates of transient local injection pain and myalgia in the 4CMenB group. No safety concerns were identified.
  
  
  CONCLUSIONS
  Although we detected no significant difference between groups at 1 month after vaccine course, MenACWY-CRM and 4CMenB vaccines reduced meningococcal carriage rates during 12 months after vaccination and therefore might affect transmission when widely implemented.
  
  
  BACKGROUND
  Novartis Vaccines.
authors.affiliation: Academic Unit of Clinical Experimental Sciences and NIHR Southampton Respiratory Biomedical Research Unit, Faculty of Medicine and Institute for Life Sciences, University of Southampton, Southampton, UK. Electronic address: R.C.Read@soton.ac.uk.
authors.forename: Robert C
authors.initials: RC
authors.lastname: Read
authors.affiliation: Faculty of Medical and Human Sciences, University of Manchester, Manchester, UK.
authors.forename: David
authors.initials: D
authors.lastname: Baxter
authors.affiliation: The James Cook University Hospital, Middlesborough, UK.
authors.forename: David R
authors.initials: DR
authors.lastname: Chadwick
authors.affiliation: Academic Unit of Clinical Experimental Sciences and NIHR Southampton Respiratory Biomedical Research Unit, Faculty of Medicine and Institute for Life Sciences, University of Southampton, Southampton, UK; Southampton NIHR Wellcome Trust Clinical Research Facility, University Hospital Southampton NHS Foundation Trust, Southampton, UK.
authors.forename: Saul N
authors.initials: SN
authors.lastname: Faust
authors.affiliation: Schools of Clinical Science and Cellular and Molecular Medicine, University of Bristol, Bristol, UK.
authors.forename: Adam
authors.initials: A
authors.lastname: Finn
authors.affiliation: Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, UK.
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Gordon
authors.affiliation: Division of Clinical Sciences, St George's, University of London, London, UK.
authors.forename: Paul T
authors.initials: PT
authors.lastname: Heath
authors.affiliation: Surrey Clinical Research Centre, University of Surrey, Guildford, UK.
authors.forename: David J M
authors.initials: DJ
authors.lastname: Lewis
authors.affiliation: Oxford Vaccine Group, Department of Paediatrics, University of Oxford and the NIHR Oxford Biomedical Centre, Oxford, UK.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Pollard
authors.affiliation: Centre for Biomolecular Sciences, University of Nottingham, Nottingham, UK.
authors.forename: David P J
authors.initials: DP
authors.lastname: Turner
authors.affiliation: Department of Infection and Immunity, University of Sheffield, Sheffield, UK.
authors.forename: Rohit
authors.initials: R
authors.lastname: Bazaz
authors.affiliation: Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, UK.
authors.forename: Amitava
authors.initials: A
authors.lastname: Ganguli
authors.affiliation: Academic Unit of Clinical Experimental Sciences and NIHR Southampton Respiratory Biomedical Research Unit, Faculty of Medicine and Institute for Life Sciences, University of Southampton, Southampton, UK; Southampton NIHR Wellcome Trust Clinical Research Facility, University Hospital Southampton NHS Foundation Trust, Southampton, UK.
authors.forename: Tom
authors.initials: T
authors.lastname: Havelock
authors.affiliation: Centre for Biomolecular Sciences, University of Nottingham, Nottingham, UK.
authors.forename: Keith R
authors.initials: KR
authors.lastname: Neal
authors.affiliation: Division of Clinical Sciences, St George's, University of London, London, UK.
authors.forename: Ifeanyichukwu O
authors.initials: IO
authors.lastname: Okike
authors.affiliation: Schools of Clinical Science and Cellular and Molecular Medicine, University of Bristol, Bristol, UK.
authors.forename: Begonia
authors.initials: B
authors.lastname: Morales-Aza
authors.affiliation: NIHR Wellcome Trust Clinical Research Facility, Manchester Royal Infirmary, Manchester, UK.
authors.forename: Kamlesh
authors.initials: K
authors.lastname: Patel
authors.affiliation: Oxford Vaccine Group, Department of Paediatrics, University of Oxford and the NIHR Oxford Biomedical Centre, Oxford, UK.
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Snape
authors.affiliation: The James Cook University Hospital, Middlesborough, UK.
authors.forename: John
authors.initials: J
authors.lastname: Williams
authors.affiliation: Public Health England, Manchester Royal Infirmary, Manchester, UK.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Gilchrist
authors.affiliation: Public Health England, Manchester Royal Infirmary, Manchester, UK.
authors.forename: Steve J
authors.initials: SJ
authors.lastname: Gray
authors.affiliation: Department of Zoology, University of Oxford, Oxford, UK.
authors.forename: Martin C J
authors.initials: MC
authors.lastname: Maiden
authors.affiliation: Novartis Vaccines and Diagnostics, Cambridge, MA, USA.
authors.forename: Daniela
authors.initials: D
authors.lastname: Toneatto
authors.affiliation: Novartis Vaccines and Diagnostics, Cambridge, MA, USA.
authors.forename: Huajun
authors.initials: H
authors.lastname: Wang
authors.affiliation: Novartis Vaccines and Diagnostics, Cambridge, MA, USA.
authors.forename: Maggie
authors.initials: M
authors.lastname: McCarthy
authors.affiliation: Novartis Vaccines and Diagnostics, Cambridge, MA, USA.
authors.forename: Peter M
authors.initials: PM
authors.lastname: Dull
authors.affiliation: Faculty of Medical and Human Sciences, University of Manchester, Manchester, UK; Public Health England, Manchester Royal Infirmary, Manchester, UK.
authors.forename: Ray
authors.initials: R
authors.lastname: Borrow
mesh_terms: D000293:Adolescent; D002353:Carrier State / Q000517:prevention & control*; D005260:Female; D006801:Humans; D008297:Male; D008589:Meningococcal Infections / Q000517:prevention & control*; D022401:Meningococcal Vaccines / Q000627:therapeutic use*; D009345:Neisseria meningitidis; D038541:Neisseria meningitidis, Serogroup B; D016037:Single-Blind Method; D055815:Young Adult
chemical_list: D022401:Meningococcal Vaccines