An open-label, phase IV randomised controlled trial of two schedules of a four-component meningococcal B vaccine in UK preterm infants.
Calvert A., Andrews N., Barlow S., Borrow R., Black C., Bromage B., Carr J., Clarke P., Collinson AC., Few K., Hayward N., Jones CE., Le Doare K., Ladhani SN., Louth J., Papadopoulou G., Pople M., Scorrer T., Snape MD., Heath PT.
ObjectiveTo compare immunological responses of preterm infants to a four-component meningococcal B vaccine (4CMenB; Bexsero) following a 2+1 vs a 3+1 schedule, and to describe reactogenicity of routine vaccines.DesignAn open-label, phase IV randomised study conducted across six UK sites.SettingNeonatal units, postnatal wards, community recruitment following discharge.Participants129 preterm infants born at a gestation of <35 weeks (64 in group 1 (2+1), 65 in group 2 (3+1)) were included in the analysis. Analysis was completed for postprimary samples from 125 participants (59 in group 1, 66 in group 2) and for postbooster samples from 118 participants (59 in both groups).InterventionsInfants randomised to 4CMenB according to a 2+1 or a 3+1 schedule, alongside routine vaccines.Main outcome measuresSerum bactericidal antibody (SBA) assays performed at 5, 12 and 13 months of age: geometric mean titres (GMTs) and proportions of infants achieving titres ≥4 compared between groups.ResultsThere were no significant differences in SBA GMTs between infants receiving a 2+1 compared with a 3+1 schedule following primary or booster vaccination, but a significantly higher proportion of infants had an SBA titre ≥4 against strain NZ98/254 (porin A) at 1 month after primary vaccination using a 3+1 compared with a 2+1 schedule (3+1: 87% (95% CI 76 to 94%), 2+1: 70% (95% CI 56 to 81%), p=0.03).At 12 weeks of age those in the 3+1 group, who received a dose of 4CMenB, had significantly more episodes of fever >38.0°C than those in the 2+1 group who did not (group 2+1: 2% (n=1); 3+1: 14% (n=9); p=0.02).ConclusionsBoth schedules were immunogenic in preterm infants, although a lower response against strain NZ98/254 was seen in the 2+1 schedule; ongoing disease surveillance is important in understanding the clinical significance of this difference.Trial registration numberNCT03125616.