Evidence map›Paper›PMID 25832102›Full record

Trial reportBMJ (Clinical research ed.)2015

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.

David Pace, Ameneh Khatami, Jennifer McKenna, Danielle Campbell, Simon Attard-Montalto, Jacqueline Birks, Merryn Voysey, Catherine White, Adam Finn, Emma Macloed and 6 more

Erratum issued Registry-linked trialOpen access · hybridAbstract readClinical Trial, Phase IVMulticenter StudyRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in BMJ (Clinical research ed.), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It is linked to trial NCT01129518 (An Open Label Randomised Controlled Study to Evaluate the Induction of Immune Memory Following Infant Vaccination With a Glycoconjugate Neisseria Meningitidis Serogroup C Vaccine and to Assess the Immunological Impact of Administering Routine Infant Immunisations in Consistent Versus Alternating Limbs), which is not on this map. Cited by 10 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed, 1 pooled it
3.2field-weighted citation impact, top 9% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT01129518 phase4completednot on this map

An Open Label Randomised Controlled Study to Evaluate the Induction of Immune Memory Following Infant Vaccination With a Glycoconjugate Neisseria Meningitidis Serogroup C Vaccine and to Assess the Immunological Impact of Administering Routine Infant Immunisations in Consistent Versus Alternating Limbs

TypeinterventionalSponsorUniversity of OxfordRan2010Enrolled404ConditionsInvasive Meningococcal DiseaseArmsGlyco-conjugate Neisseria meningitidis serogroup C (MenC) vaccine, Routine schedule immunisations except monovalent MenC vaccine
3 · Its place in the literature

Who cites it

10 citing papers in PubMed, 1 synthesis or guideline pooled it, 29 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Article
  4. Article
  5. Review
  6. Article
  7. The epidemiology of invasive meningococcal disease and the utility of vaccination in Malta.European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology · 2020
    Article
  8. Article
  9. Polysaccharide structure dictates mechanism of adaptive immune response to glycoconjugate vaccines.Proceedings of the National Academy of Sciences of the United States of America · 2019
    Article
  10. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

16 authors at 6 institutions in 2 countries.

David PaceMalta Children's Vaccine Group, Mater Dei Hospital, Tal-Qroqq, Msida, MSD 2090, Malta dpace@go.net.mt.
Ameneh KhatamiOxford Vaccine Group, Department of Paediatrics, University of Oxford and the NIHR Oxford Biomedical Research Centre, Oxford, UK.
Jennifer McKennaOxford Vaccine Group, Department of Paediatrics, University of Oxford and the NIHR Oxford Biomedical Research Centre, Oxford, UK.
Danielle CampbellOxford Vaccine Group, Department of Paediatrics, University of Oxford and the NIHR Oxford Biomedical Research Centre, Oxford, UK.
Simon Attard-MontaltoMalta Children's Vaccine Group, Mater Dei Hospital, Tal-Qroqq, Msida, MSD 2090, Malta.
Jacqueline BirksCentre for Statistics in Medicine, NIHR Oxford Biomedical Research Centre, University of Oxford, Oxford, UK.
Merryn VoyseyPrimary Care Clinical Trials Unit, Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK.
Catherine WhiteBristol Children's Vaccine Centre, University Hospitals Bristol NHS Foundation Trust and University of Bristol, Bristol, UK.
Adam FinnBristol Children's Vaccine Centre, University Hospitals Bristol NHS Foundation Trust and University of Bristol, Bristol, UK.
Emma MacloedSouthampton NIHR Wellcome Trust Clinical Research Facility, University Hospital Southampton NHS Foundation Trust, Southampton, UK.
Saul N FaustSouthampton 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.
Alison Louise KentSt George's Vaccine Institute, St George's University of London, London, UK.
Paul T HeathSt George's Vaccine Institute, St George's University of London, London, UK.
Ray BorrowVaccine Evaluation Unit, Public Health England, Public Health Laboratory Manchester, Manchester Royal Infirmary, Manchester, UK.
Matthew D SnapeOxford Vaccine Group, Department of Paediatrics, University of Oxford and the NIHR Oxford Biomedical Research Centre, Oxford, UK.
Andrew J PollardOxford Vaccine Group, Department of Paediatrics, University of Oxford and the NIHR Oxford Biomedical Research Centre, Oxford, UK.
University of Oxford · GBMater Dei Hospital · MTOxford BioMedica (United Kingdom) · GBUniversity Hospitals Bristol NHS Foundation Trust · GBWellcome Trust · GBPublic Health England · GB

Funding

Wellcome Trust
6 · The paper itself

Abstract

objectiveTo 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.

designPhase IV open label randomised controlled trial carried out from July 2010 until August 2013

settingFour centres in the United Kingdom and one centre in Malta.

participantsHealthy infants aged 6-12 weeks followed up until age 24 months.

interventionsIn 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.

main outcome measureMenC 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.

resultsThe 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.

conclusionsMenC 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).

Indexed as

Immunization ScheduleImmunization, SecondaryChild, PreschoolFemaleFollow-Up StudiesHumansInfantMaleMaltaMeningococcal VaccinesModels, StatisticalSerum Bactericidal Antibody AssayUnited KingdomVaccines, ConjugateMeningococcal Vaccinesserogroup C meningococcal conjugate vaccineVaccines, Conjugate

Identifiers

PMID25832102
PMCPMC4382115
OpenAlexW2065339964

What OpenQuestion holds

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.