Background: MenACWY-7B is a pentavalent meningococcal vaccine comprising antigenic components from established vaccines MenACWY-CRM and 4-component MenB (4CMenB), and 3 additional MenB antigen components.
Aim/Methods: This completed phase 1/2 study (NCT04886154) was designed to assess the safety, effectiveness, and immunogenicity of MenACWY-7B in healthy adults 18–40 years of age (phase 1) and healthy adolescents and adults 10–25 years of age (phase 2). Phase 2 participants were randomized to receive a formulation containing either a low (MenACWY-7B-low) or high dose (MenACWY-7B-high) of the novel antigen components as 2 vaccine doses given either 2 (0,2-month) or 6 months (0,6-month) apart, or control vaccines (MenACWY-CRM + 4CMenB). Effectiveness was evaluated using endogenous complement human serum bactericidal assay (hSBA) against 110 serogroup B invasive disease strains. Immunogenicity was measured with standard hSBA.
Results: Phase 1 (n=32) was completed without safety issues. In phase 2 (n=1052), both formulations and schedules of MenACWY-7B were well tolerated. Reactogenicity and safety profiles were similar to control vaccines, and no safety issues were identified. Both formulations and schedules demonstrated immunological non-inferiority against serogroups ACWY compared with MenACWY-CRM (two-sided 97.5% CI for the difference above -10% margin). Both formulations also showed higher MenB effectiveness compared with 4CMenB at a 0,6-month schedule; however, the predetermined superiority criterion was not met (two-sided 97.5% CI for the difference not above the prespecified +5% margin), as effectiveness in the control group was higher than expected. At a 0,6-month schedule, the percentage of participants with ≥90% serogroup B strains killed was 71.2% for MenACWY-7B-low, 70.7% for MenACWY-7B-high, and 52.3% for control. For both formulations (0,6-month schedule), the percentages of participants with a 4-fold rise in hSBA titers were comparable to 4CMenB control for the MenB antigens common to both vaccines, and were higher than control for the 3 novel antigens. Immune response for all MenB antigens was higher with the 0,6-month vs. 0,2-month schedule.
Conclusions: These results demonstrate the added value of the new antigen components in MenACWY-7B. An increase in the interval between MenACWY-7B vaccinations was associated with an increase in the effectiveness and immunological response of MenACWY-7B.
Funding: GSK.