A phase 2 randomized controlled trial of a multicomponent meningococcal serogroup B vaccine, 4CMenB, in infants (II)

Abstract

The licensed meningococcal serogroup B vaccine, 4CMenB (Bexsero(®)), contains recombinant membrane proteins (rMenB) and outer membrane vesicles (OMV) of the New Zealand serogroup B strain. We investigated whether reducing the OMV and/or protein content influences 4CMenB immunogenicity and reactogenicity in healthy two month-old infants. Six formulations were studied: 4CMenB, rMenB with 0, ¼ or ½ the OMV dose in 4CMenB, a half-dose of 4CMenB or a prelicensure formulation of 4CMenB, as a 4-dose primary/booster series, concomitantly with routine vaccines (DTaP-HBV-IPV/Hib and 7-valent pneumococcal conjugate) at 2, 3, 4 and 12 months of age. Immunogenicity was assessed as serum bactericidal activity measured with human complement (hSBA) against indicator strains for Men B vaccine antigens before and after the 2,3,4-month series and 12-month dose. Parents recorded solicited reactions for 7 days after each vaccination, and any adverse events throughout the study period. All formulations elicited robust immune response against rMenB components at 5 months, there was some evidence of OMV and protein dose-dependence for Men B indicator strains tested. Titers waned up to the 12-month dose, which elicited further strong responses, which were still OMV and protein dose-dependent. Groups with no, or low-dose OMV displayed slightly lower reactogenicity profiles, but all formulations were generally well-tolerated, high fever was rare and transient, and only three transient SAEs were considered possibly vaccine-related. Decreasing or removing the OMV content reduced reactogenicity of 4CMenB to a certain extent, but had an unacceptable negative impact on the immunogenicity profile. Trial: Clinicaltrials.gov NCT00937521.

Keywords: infants; meningococcal; outer membrane vesicles; serogroup B; vaccination.

Figures

Figure 1. Study flowchart

Figure 2. Percentages of subjects in each group (with 95% CI bars) with hSBA titers ≥ 5 against three indicator serogroup B strains for fHbp, NadA and NZ OMV antigens before vaccination, one month after the third dose, before the booster dose at 12 mo and one month after the booster dose in the six study groups.

Figure 3. Percentages of subjects in each group with at least one report of any reaction, a local reaction or a systemic reaction after each vaccination in the six study groups