Immunogenicity and safety of investigational vaccine formulations against meningococcal serogroups A, B, C, W, and Y in healthy adolescents

Abstract

This phase 2 study assessed the immunogenicity, safety, and reactogenicity of investigational formulations of meningococcal ABCWY vaccines, consisting of recombinant proteins (rMenB) and outer membrane vesicle (OMV) components of a licensed serogroup B vaccine, combined with components of a licensed quadrivalent meningococcal glycoconjugate vaccine (MenACWY-CRM). A total of 495 healthy adolescents were randomized to 6 groups to receive 2 doses (Months 0, 2) of one of 4 formulations of rMenB antigens, with or without OMV, combined with MenACWY-CRM, or 2 doses of rMenB alone or one dose of MenACWY-CRM then a placebo. Immunogenicity was assessed by serum bactericidal assay with human complement (hSBA) against serogroups ACWY and serogroup B test strains; solicited reactions and any adverse events (AEs) were assessed. Two MenABCWY vaccinations elicited robust ACWY immune responses, with higher seroresponse rates than one dose of MenACWY-CRM. Bactericidal antibody responses against the rMenB antigens and OMV components were highest in subjects who received 2 doses of OMV-containing MenABCWY formulations, with ≥68% of subjects achieving hSBA titers ≥5 against each of the serogroup B test strains. After the first dose, solicited local reaction rates were higher in the MenABCWY or rMenB groups than the MenACWY-CRM group, but similar across groups after the second dose, consisting mainly of transient injection site pain. Fever (≥38.0°C) was rare and there were no vaccine-related serious AEs. In conclusion, investigational MenABCWY formulations containing OMV components elicited highly immunogenic responses against meningococcal serogroups ACWY, as well as serogroup B test strains, with an acceptable safety profile. [NCT01210885].

Keywords: AE, adverse event; CI, confidence interval; GMT, geometric mean titer; IMD, invasive meningococcal disease; NHBA, Neisserial Heparin Binding Antigen; NadA, Neisseria adhesin A; Neisseria meningitidis; OMV, outer membrane vesicle; PP, per-protocol set; SAE, serious adverse event; adolescents; conjugate vaccine; fHbp, factor H-binding protein; hSBA, serum bactericidal assay with human complement; immunogenicity; meningococcal disease; safety.

Figures

Figure 1.

Subject disposition flowchart.

Figure 2.

(A) Percentage of subjects (95% CI) with seroresponse and percentage of subjects (95% CI) with hSBA titers ≥8 against serogroups ACWY at one month after first dose (Day 31) and 1 month after the second dose (Day 91), by vaccination group. (B) hSBA geometric mean titers (95% CI) against serogroups ACWY at baseline (Day 1) and one month after the first and second doses, by vaccination group.

Figure 3.

(A) Percentage of subjects (95% CI) with hSBA titers ≥5 and (B) hSBA geometric mean titers (95% CI) for serogroup B test strains 44/76-SL (fHbp), 5/99 (NadA), M07–0241084 (NHBA) and NZ98/254 (PorA) at baseline (Day 1), one month after the first dose (Day 31), and one month after the second dose (Day 91), by vaccination group.