Use of an investigational multicomponent meningococcal serogroup B vaccine (4CMenB) in a clinical trial in 3630 infants

Background Protecting infants against serogroup B meningococcal disease is a long-standing public health need. An investigational multicomponent vaccine (4CMenB) containing three recombinant proteins identified using whole-genome sequencing and outer membrane vesicles from the New Zealand outbreak strain was evaluated in healthy infants. Methods Healthy infants were randomised to receive routine infant vaccines alone, with one of three 4CMenB lots, or with serogroup C conjugate vaccine at 2, 4, 6 months of age. In an open-label cohort, 4CMenB was assessed via serum bactericidal assay using human complement (hSBA) against serogroup B test strains. Noninferiority criteria for seroresponse to routine vaccines were predefined. In open-label and observer-blind cohorts, prespecified solicited injection site and systemic reactions within 7 days of vaccination were evaluated. Adverse events were monitored. Results Overall 3630 infants enrolled. All lots of 4CMenB had consistent immunogenicity, and 100% of 4CMenB recipients had protective titers to at least two heterologous serogroup B strains. Responses to 4CMenB and routine vaccines were consistent with protection; no evidence of interference with co-administration of 4CMenB was noted for any antigen except Polio 2. Participants receiving 4CMenB and the routine vaccines showed evidence of increased reactogenicity compared with those receiving routine vaccines only or those receiving MenC and routine vaccines. Parents of infants in the observer-blind cohort were more likely to seek medical attention for fever than were those in the open-label cohort. Conclusion In this study, 4CMenB showed a very promising immunogenicity profile and acceptable reactogenicity in infants.