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

Mildred A. Iro, Matthew D. Snape, Merryn Voysey, Sena Jawad, Adam Finn, Paul T. Heath, Gianni Bona, Susanna Esposito, Javier Diez-Domingo, Roman Prymula, Adefowope Odueyungbo, Daniela Toneatto, Peter Dull, Andrew J. Pollard

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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 24 months and characterised the antibody response to a fifth dose administered at 4 years 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, 6 month 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 4 years 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 12–36 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.
Original languageEnglish
Pages (from-to)395-402
Number of pages8
JournalVaccine
Volume35
Issue number2
Early online date30 Nov 2016
DOIs
Publication statusPublished - 5 Jan 2017

Keywords

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

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    Iro, M. A., Snape, M. D., Voysey, M., Jawad, S., Finn, A., Heath, P. T., Bona, G., Esposito, S., Diez-Domingo, J., Prymula, R., Odueyungbo, A., Toneatto, D., Dull, P., & Pollard, A. J. (2017). Persistence of bactericidal antibodies following booster vaccination with 4CMenB at 12, 18 or 24 months and immunogenicity of a fifth dose administered at 4 years of age-a phase 3 extension to a randomised controlled trial. Vaccine, 35(2), 395-402. https://doi.org/10.1016/j.vaccine.2016.11.009