Immunogenicity and safety of the multicomponent meningococcal B vaccine (4CMenB) in children and adolescents: a systematic review and meta-analysis

Background: The multicomponent meningococcal serogroup B vaccine (4CMenB) has been licensed in more than 35 countries. However, uncertainties remain about the lowest number of doses required to induce satisfactory, persistent immune responses. We did a systematic review and meta-analysis to provide quantitative estimates for the immunogenicity, persistence of immunogenicity, and safety of 4CMenB vaccine in children and adolescents. Methods: For this systematic review and meta-analyses (proportion, head to head, and network), we searched MEDLINE, Scopus, Embase, and ClinicalTrials.gov from database inception to June 30, 2017, for randomised trials that compared the immunogenicity or safety of the 4CMenB vaccine with its originator meningococcal B recombinant vaccine or routine vaccines in children or adolescents. For proportion meta-analyses, we also included single arm trials and follow-up studies of randomised controlled trials. Trials that assessed immunogenicity against at least one of four Neisseria meningitidis serogroup B reference strains (44-76/SL, 5/99, NZ98/254, and M10713) and included participants younger than 18 years who had received two or more doses of the 4CMenB vaccine were eligible for inclusion. We requested individual patient-level data from study authors and extracted data from published reports and online trial registries. We did meta-analyses to assess 4CMenB safety and immunogenicity against the four reference strains 30 days after a primary immunisation course (three doses for children, two doses for adolescents), 30 days after the primary course plus one booster dose (children only), 6 months or more after primary course, and 6 months or more after the booster dose. Findings: 736 non-duplicate records were screened, and ten randomised trials and eight follow-on extension trials on 4CMenB met the inclusion criteria. In intention-to-treat analyses, the overall proportion of children and adolescents who achieved seroconversion 30 days after the primary course of 4CMenB was 92% (95% CI 89–95 [I 2 =95%, p<0·0001]) for the 44/76-SL strain, 91% (87–95 [I 2 =95%, p<0·0001]) for the 5/99 strain, 84% (77–90 [I 2 =97%, p<0·0001]) for the NZ98-254 strain, and 87% (68–99 [I 2 =97%, p<0·0001]) for the M10713 strain. 6 months after the primary course, the immunogenicity remained adequate to high against all three tested strains (5/99, 44/76-SL, and NZ98/254) in adolescents (≥77%), and against two of four strains (5/99 and 44/76-SL) in children (≥67%): the proportion of patients who achieved seroconversion substantially declined for M10713 (<50%) and NZ98/254 (