Immunogenicity and tolerability of recombinant serogroup B meningococcal vaccine administered with or without routine infant vaccinations according to different immunization schedules: a randomized controlled trial.
BACKGROUND
In the absence of an effective vaccine, serogroup B Neisseria meningitidis (MenB) remains a major cause of invasive disease in early childhood in developed countries.


OBJECTIVE
To determine the immunogenicity and reactogenicity of a multicomponent MenB vaccine (4CMenB) and routine infant vaccines when given either concomitantly or separately.


METHODS
Phase 2b, multicenter, open-label, parallel-group, randomized controlled study of 1885 infants enrolled at age 2 months from August 2008 to July 2010 in Europe.


METHODS
Participants were randomized 2:2:1:1 to receive (1) 4CMenB at 2, 4, and 6 months with routine vaccines (7-valent pneumococcal and combined diphtheria, tetanus, acellular pertussis, inactivated polio, hepatitis B, Haemophilus influenzae type b vaccines); (2) 4CMenB at 2, 4, and 6 months and routine vaccines at 3, 5, and 7 months; (3) 4CMenB with routine vaccines at 2, 3, and 4 months; or (4) routine vaccines alone at 2, 3, and 4 months.


METHODS
Percentage of participants with human complement serum bactericidal activity (hSBA) titer of 1:5 or greater against 3 MenB strains specific for vaccine antigens (NZ98/254, 44/76-SL, and 5/99).


RESULTS
After three 4CMenB vaccinations, 99% or more of infants developed hSBA titers of 1:5 or greater against strains 44/76-SL and 5/99. For NZ98/254, this proportion was 79% (95% CI, 75.2%-82.4%) for vaccination at 2, 4, and 6 months with routine vaccines, 86.1% (95% CI, 82.9%-89.0%) for vaccination at 2, 4, and 6 months without routine vaccines, and 81.7% (95% CI, 76.6%-86.2%) for vaccination at 2, 3, and 4 months with routine vaccines. Responses to routine vaccines given with 4CMenB were noninferior to routine vaccines alone for all antigens, except for the responses to pertactin and serotype 6B pneumococcal polysaccharide. Fever was seen following 26% (158/602) to 41% (247/607) of 4CMenB doses when administered alone, compared with 23% (69/304) to 36% (109/306) after routine vaccines given alone and 51% (306/605) to 61% (380/624) after 4CMenB and routine vaccines administered together.


CONCLUSIONS
A 4CMenB vaccine is immunogenic against reference strains when administered with routine vaccines at 2, 4, and 6 or at 2, 3, and 4 months of age, producing minimal interference with the response to routine infant vaccinations.


BACKGROUND
clinicaltrials.gov Identifier: NCT00721396.
Oxford Vaccine Group, NIHR Oxford Biomedical Research Centre and Department of Paediatrics, University of Oxford, Oxford, United Kingdom.
Nicoletta
N
Gossger
Matthew D
MD
Snape
Ly-Mee
LM
Yu
Adam
A
Finn
Gianni
G
Bona
Susanna
S
Esposito
Nicola
N
Principi
Javier
J
Diez-Domingo
Etienne
E
Sokal
Birgitta
B
Becker
Dorothee
D
Kieninger
Roman
R
Prymula
Peter
P
Dull
Ellen
E
Ypma
Daniela
D
Toneatto
Alan
A
Kimura
Andrew J
AJ
Pollard
D000917:Antibody Formation; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007115:Immunization Schedule; D007223:Infant; D008297:Male; D008589:Meningococcal Infections / Q000517:prevention & control*; D022401:Meningococcal Vaccines / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology*; D009345:Neisseria meningitidis; D058248:Serum Bactericidal Antibody Assay; D014612:Vaccines / Q000008:administration & dosage; D014614:Vaccines, Synthetic / Q000276:immunology
C570015:4CMenB vaccine; D022401:Meningococcal Vaccines; D014612:Vaccines; D014614:Vaccines, Synthetic