British Medical Journal
09 May 2015(vol 350, issue 8007)
http://www.bmj.com/content/350/8007

.

Research
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
BMJ 2015; 350 doi: http://dx.doi.org/10.1136/bmj.h1554 (Published 01 April 2015) Cite this as: BMJ 2015;350:h1554
David Pace, consultant infectious disease paediatrician1, Ameneh Khatami, clinical lecturer2,
Jennifer McKenna, senior research nurse2, Danielle Campbell, research nurse2, Simon Attard-Montalto, consultant paediatrician1, Jacqueline Birks, senior medical statistician3, Merryn Voysey, senior trial statistician4, Catherine White, paediatric clinical research nurse5, Adam Finn, professor of paediatrics5, Emma Macloed, paediatric clinical research nurse6, Saul N Faust, professor of paediatric immunology and infectious diseases67, Alison Louise Kent, clinical research fellow8, Paul T Heath, professor/consultant paediatric infectious diseases8, Ray Borrow, consultant clinical scientist/professor of vaccine preventable diseases9, Matthew D Snape, consultant in vaccinology and general paediatrics2, Andrew J Pollard, professor of paediatric infection and immunity2
Author affiliations
Accepted 17 February 2015
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.
Design 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.
Participants
Healthy infants aged 6-12 weeks followed up until age 24 months.
Interventions 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.
Main outcome measure
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).