Background: MenB-FHbp (bivalent rLP2086), which targets meningococcal serogroup B (MnB) factor H binding proteins (fHBP), was the first vaccine approved in the US to prevent MnB disease in persons aged 1025 years. US-specific data in adolescents are particularly relevant because of MnB outbreaks on US college campuses. FDA approved the vaccine through an accelerated process using a serologic surrogate for efficacy that demonstrated vaccine induction of bactericidal antibodies against MnB strains expressing diverse fHBPs. Immunogenicity data are presented from a confirmatory pivotal phase 3 trial of MenB-FHbp, in which half of subjects were enrolled in the US, to extend phase 2 data, the basis for accelerated approval in the US.
Methods: Healthy subjects aged 10<19 years were randomized to receive 1 of 3 lots of (MenB-FHbp) at 0, 2, and 6 months, or hepatitis A virus vaccine at 0 and 6 months and saline at 2 months. Immune responses were assessed by serum bactericidal assays using human complement (hSBAs) with 4 primary MnB test strains expressing vaccine-heterologous fHBP variants. Coprimary immunogenicity endpoints were proportion of subjects with a ≥4-fold increase in hSBA titers from baseline for each test strain and proportion achieving hSBA titers ≥ lower limit of quantification for all 4 test strains combined (composite response) after dose 3. Lot consistency was assessed with hSBA geometric mean titers (GMTs) for 2 primary MnB test strains after dose 3 (2-fold margin for equivalence). The study was powered to assess immunogenicity in US and total populations.
Results: 50.2% of subjects were enrolled in the US. 1359 US subjects received MenB-FHbp. 81.9%92.0% of subjects had ≥4-fold rise in hSBA titers from baseline to 1 month after dose 3 against each primary strain (Figure); 85.7% achieved a composite response after dose 3. Corresponding results after dose 2 were 55.5%87.3% and 50.5%, respectively. hSBA GMTs were similar for all 3 vaccine lots (GMT ratio range: 0.871.04). Lower confidence interval threshold criteria were achieved for US subjects; thus coprimary endpoints were met.
Conclusion: As in the global study, MenB-FHbp elicited robust and broad immune responses in US adolescents after 3 doses. Vaccine lots were similar.
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