A novel combined Hib-MenC-TT glycoconjugate vaccine as a booster dose for toddlers: a phase 3 open randomised controlled trial.
OBJECTIVE
To study the immunogenicity and reactogenicity of a combined Haemophilus influenzae type b and Neisseria meningitidis serogroup C tetanus toxoid conjugate vaccine (Hib-MenC-TT) when administered as a booster dose in combination with a measles, mumps and rubella vaccine (MMR).


METHODS
A phase 3 open randomised controlled trial.


METHODS
One centre in Oxford, UK and nine centres in Poland.


METHODS
12-15-month-old healthy children.


METHODS
In the primary stage of the study 500 healthy 6-12-week-old infants were randomised in a 3:1 ratio to receive Hib-MenC-TT+DTPa-IPV or MenC-CRM197 vaccine+DTPa-IPV-Hib. In the booster stage, 476 participants (190 in the UK and 286 in Poland) were vaccinated with Hib-MenC-TT and MMR.


METHODS
The proportion of children with protective serum antibody levels against MenC and Hib 6 weeks following a Hib-MenC-TT booster dose.


RESULTS
The co-primary objectives were met: the Hib-MenC-TT booster dose induced protective antibody titres in children vaccinated with Hib-MenC-TT+DTPa-IPV or MenC-CRM197+DTPa-IPV-Hib at 2, 3 and 4 months of age. 94.8% (lower limit of (LL) 95% CI 92.4) of participants had rSBA-MenC >or=1:128 and 100% (LL 95% CI 99.2) achieved anti-PRP concentrations >or=1.0 microg/ml. The percentage of toddlers with a post boost rSBA-MenC of 1:128 was significantly higher after priming with Hib-MenC-TT (97.7%) than after MenC-CRM197 (86%) (difference: 11.7%; 95% CI 6.2 to 19.4).


CONCLUSIONS
The waning antibody titres against Hib and MenC following primary immunisation can be boosted to protective levels by administering the Hib-MenC-TT vaccine at 12-15 months of age, supporting the recent introduction of this vaccine in the UK immunisation schedule to sustain protection of children against Hib and MenC disease.


BACKGROUND
NCT00258700. Study ID: 103974 (http://clinicaltrials.gov).
Pace
D
D
Oxford Vaccine Group, Centre for Clinical Vaccinology and Tropical Medicine, Department of Paediatrics, University of Oxford, Churchill Hospital, Headington, Oxford, UK. dpace@mail.global.net.mt
Snape
M
M
Westcar
S
S
Oluwalana
C
C
Yu
L-M
LM
Begg
N
N
Wysocki
J
J
Czajka
H
H
Maechler
G
G
Boutriau
D
D
Pollard
A J
AJ
D000907:Antibodies, Bacterial / Q000096:biosynthesis / Q000097:blood; D000914:Antibodies, Viral / Q000096:biosynthesis; D005260:Female; D006192:Haemophilus Infections / Q000517:prevention & control; D018073:Haemophilus Vaccines / Q000009:adverse effects / Q000276:immunology*; D019741:Haemophilus influenzae type b / Q000276:immunology; D006801:Humans; D007115:Immunization Schedule; D007117:Immunization, Secondary / Q000009:adverse effects; D007223:Infant; D008297:Male; D022542:Measles-Mumps-Rubella Vaccine / Q000009:adverse effects / Q000276:immunology; D008585:Meningitis, Meningococcal / Q000517:prevention & control; D038542:Neisseria meningitidis, Serogroup C / Q000276:immunology; D011044:Poland; D013745:Tetanus Toxoid / Q000009:adverse effects / Q000276:immunology*; D006113:United Kingdom; D018074:Vaccines, Conjugate / Q000009:adverse effects / Q000276:immunology
D000907:Antibodies, Bacterial; D000914:Antibodies, Viral; D018073:Haemophilus Vaccines; C527605:Hib-MenCY-TT vaccine; D022542:Measles-Mumps-Rubella Vaccine; D013745:Tetanus Toxoid; D018074:Vaccines, Conjugate