4CMenB Breadth of Immune Response, Immunogenicity, and Safety: Results from a Phase 3 Randomized, Controlled, Observer Blind Study in Adolescents and Young Adults

Abstract

Abstract Background Meningococcal serogroup B (MenB) strains are highly diverse. Breadth of immune response for the MenB vaccine, 4CMenB, administered at 0-2, 0-6, or 0-2-6 months, was demonstrated by endogenous complement-human serum bactericidal antibody (enc-hSBA) assay against an epidemiologically-relevant panel of 110 MenB strains. Methods In a phase 3 trial, 3651 healthy 10–25 year-old participants were randomized 5:5:9:1 to receive 4CMenB (0-6 schedule), 4CMenB (0-2-6 schedule), investigational MenABCWY vaccine, or control MenACWY-CRM vaccine. The primary objectives were to evaluate safety and demonstrate breadth of immune response by enc-hSBA assay against the MenB strain panel using test-based (percentage of samples without bactericidal activity against strains after 4CMenB versus control vaccination) and responder-based (percentage of participants whose post-vaccination sera kill ≥70% strains) approaches. Success was demonstrated with two-sided 97.5% confidence interval (CI) lower limit >65%. Immunogenicity was assessed by traditional hSBA assay against four indicator strains. Results Breadth of immune response (test-based) was 78.7% (97.5% CI 77.2%–80.1%), 81.8% (80.4%–83.1%), 83.2% (81.9%–84.4%) for the 0-2, 0-6, and 0-2-6 schedules, respectively, and (responder-based) 84.8% (81.8%–87.5%), 89.8% (87.2%–92.0%), and 93.4% (91.2%–95.2%), respectively. No clinically relevant differences in immunogenicity were observed across schedules. 4CMenB was well tolerated. Conclusions The two-dose (0-2, 0-6) 4CMenB schedules met pre-defined criteria for success for both breadth of immune response endpoints against a diverse MenB strain panel, had comparable immunogenicity, and safety in line with the established 4CMenB safety profile. The three-dose schedule provided no additional immunological benefit, supporting use of the 4CMenB 0-2 schedule. Clinical Trial Registration NCT04502693.