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Vaccine. 2017 Jan 5;35(2):395-402. doi: 10.1016/j.vaccine.2016.11.009. Epub 2016 Nov 30.

Persistence of bactericidal antibodies following booster vaccination with 4CMenB at 12, 18 or 24months and immunogenicity of a fifth dose administered at 4years of age-a phase 3 extension to a randomised controlled trial.

Author information

1
Oxford Vaccine Group, Department of Paediatrics, University of Oxford and the NIHR Oxford Biomedical Research Centre, Oxford, UK. Electronic address: mildred.iro@paediatrics.ox.ac.uk.
2
Oxford Vaccine Group, Department of Paediatrics, University of Oxford and the NIHR Oxford Biomedical Research Centre, Oxford, UK.
3
Oxford Vaccine Group, Department of Paediatrics, University of Oxford and the NIHR Oxford Biomedical Research Centre, Oxford, UK; Nuffield Department of Primary Health Care Health Sciences, University of Oxford, Oxford, UK.
4
Nuffield Department of Primary Health Care Health Sciences, University of Oxford, Oxford, UK.
5
Bristol Children's Vaccine Centre, University of Bristol, Bristol, UK.
6
St Georges Vaccine Institute, St George's, University of London, London, UK.
7
Azienda Ospedaliero-Universitaria Maggiore della Carità, Clinica Pediatrica, Novara, Italy.
8
Pediatric Highly Intensive Care Unit, Università degli Studi di Milano, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
9
Vaccine Research Area, Fundación para el Fomento de la Investigación Sanitaria y Biomédica (FISABIO), Valencia, Spain.
10
Charles University Prague, School of Medicine Hradec Kralove, Czech Republic.
11
Novartis Vaccines and Diagnostics Inc., Cambridge, MA, USA.
12
GSK Vaccines S.r.l., Siena, Italy.

Abstract

BACKGROUND:

4CMenB is immunogenic in infants and toddlers. We assessed persistence of human complement serum bactericidal activity (hSBA) following a fourth dose administered at 12, 18 or 24months and characterised the antibody response to a fifth dose administered at 4years of age.

METHODS:

A phase 3, open label, multi-centre extension to a randomised controlled trial conducted in four countries (number of centres): Czech Republic (nineteen), Italy (four), Spain (four) and the United Kingdom (four). Four-year-old children who were either 4CMenB-naïve or had previously received a variety of 3-dose infant priming schedules and a booster vaccine as toddlers (follow-on group) were recruited. Venous blood samples were obtained to determine hSBA against four reference strains; acting as targets to assess immunity to each of the vaccine antigens, NadA (5/99), fHbp (H44/76), PorA (NZ98/254), and NHBA (M10713) at baseline (prior to vaccination, all participants) and one month following a dose of 4CMenB for all vaccine-naïve and follow-on participants primed with the 2, 3, 4 schedule, and a third of follow-on participants primed with a 2, 4, 6month schedule.

RESULTS:

At baseline (prior to vaccination), the proportion of participants (n=468) with hSBA titers⩾5 was similar across all followon groups: 89-100% against 5/99; 12-35% for H44/76; 8-12% for NZ98/254 and 53-80% for M10713 compared with 5%, 0%, 0%; and 60% respectively, for the vaccine-naïve controls (n=206). Following a dose of 4CMenB at 4years of age, this increased to 100% (5/99), 97-100% (H44/76), 80-95 % (NZ98/254) and 84-100% (M10713) (n=210), compared with 89%, 70%, 24%, and 76% respectively for vaccine-naïve controls (n=192).

CONCLUSION:

Waning of protective antibodies occurred 24–36 months after toddler booster regardless of age at boost. This was least marked against target strains 5/99 and M10713. A robust memory response occurred after a booster dose given at 4 years of age.

KEYWORDS:

4CMenB; MenW; Neisseria meningitidis; Reactogenicity; Toddler; Vaccine

PMID:
27914744
DOI:
10.1016/j.vaccine.2016.11.009
[Indexed for MEDLINE]
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