title: 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.
authors.affiliation: a Pediatric Highly Intensive Care Unit; Department of Pathophysiology and Transplantation; University of Milan, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico; Milan, Italy.
authors.forename: Susanna
authors.initials: S
authors.lastname: Esposito
authors.forename: Roman
authors.initials: R
authors.lastname: Prymula
authors.forename: Gian Vincenzo
authors.initials: GV
authors.lastname: Zuccotti
authors.forename: Fang
authors.initials: F
authors.lastname: Xie
authors.forename: Michelangelo
authors.initials: M
authors.lastname: Barone
authors.forename: Peter M
authors.initials: PM
authors.lastname: Dull
authors.forename: Daniela
authors.initials: D
authors.lastname: Toneatto
mesh_terms: D000942:Antigens, Bacterial / Q000276:immunology* / Q000633:toxicity*; D001770:Blood Bactericidal Activity; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology* / Q000473:pathology; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D022401:Meningococcal Vaccines / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology*; D038541:Neisseria meningitidis, Serogroup B / Q000276:immunology*
chemical_list: C570015:4CMenB vaccine; D000942:Antigens, Bacterial; D022401:Meningococcal Vaccines
keywords: infants; meningococcal; outer membrane vesicles; serogroup B; vaccination