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

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.