Meningococcal ACWYX conjugate vaccine in 2–29 year-olds in Mali and Gambia

BACKGROUND: An effective, affordable, multivalent meningococcal conjugate vaccine is needed to prevent epidemic meningitis in the African meningitis belt. This trial assessed the safety and immunogenicity of NmCV-5, a pentavalent ACWYX vaccine. METHODS: We conducted a phase 3, non-inferiority trial in healthy 2-29-year-olds in Mali and The Gambia. Participants were randomly assigned, 2:1, to receive a single intramuscular dose of NmCV-5 or MenACWY-D (Menactra). Immunogenicity was assessed at day 28. The non-inferiority of NmCV-5 compared to MenACWY-D was assessed based on differences in seroresponse rates (lower bound of 96% CI above −10%) or geometric mean titre (GMT) ratios (lower bound of 98.98% CI above 0.5). Serogroup X responses were compared to the lowest response to MenACWY-D serogroups. RESULTS: 1800 participants received NmCV-5 or MenACWY-D. NmCV-5 seroresponse rates ranged from 70.5% (95% CI 67.8–73.2) for serogroup A to 98.5% (95% CI 97.6–99.2) for serogroup W and serogroup X seroresponse rate was 97.2% (95% CI 96.0–98.1). The overall difference in seroresponse rates (NmCV-5–MenACYW-D) for the shared serogroups ranged from 1.2% (96%CI −0.3–3.1) for serogroup W to 20.5% (96%CI 15.4–25.6) for serogroup A. The overall GMT ratios (NmCV-5/MenACYW-D) for shared serogroups ranged from 1.7 (98.98%CI 1.5–1.9) for serogroup A to 2.8 (98.98%CI 2.3–3.5) for serogroup C. The serogroup X component of NmCV-5 generated seroresponses and GMTs that met the pre-specified non-inferiority criteria. Systemic adverse events were similar between groups (11.1% NmCV-5 and 9.2% MenACWY-D). CONCLUSIONS: NmCV-5 elicits comparable immune responses to all 4 serotypes in common with MenACWY-D as well as to serogroup X without evident safety concerns.