title: Immunogenicity and safety of three doses of a bivalent (B:4:p1.19,15 and B:4:p1.7-2,4) meningococcal outer membrane vesicle vaccine in healthy adolescents.
abstract: An experimental bivalent meningococcal outer membrane vesicle (OMV) vaccine (B:4:P1.19,15 and B:4:P1.7-2,4) has been developed to provide wide vaccine coverage particularly of the circulating strains in Europe. A randomized, controlled phase II study (study identification number, 710158/002; ClinicalTrials.gov identifier number, NCT00137917) to evaluate the immunogenicity and safety of three doses of the OMV vaccine when given to healthy 12- to 18-year-olds on a 0-2-4 month (n = 162) or 0-1-6 month schedule (n = 159). A control group received two doses of hepatitis A and one of conjugated meningococcal serogroup C vaccine on a 0-1-6 month schedule (n = 157). Immune response, defined as a fourfold increase in serum bactericidal titer using a range of vaccine-homologous or PorA-related and heterologous strains, was determined for samples taken before and 1 month after vaccination; assays were performed at two laboratories. As measured at the GlaxoSmithKline (GSK) laboratory, the OMV vaccine induced an immune response against homologous or PorA-related strains (in at least 51% of subjects against strains of serosubtype P1.19,15 and at least 66% against strains of serosubtype P1.7-2,4) and against a set of three heterologous strains (in 28% to 46% of subjects). Both laboratories showed consistent results for immune response rates. The OMV vaccine had a similar reactogenicity profile for each schedule. Pain preventing normal activities occurred in approximately one-fifth of the subjects; this was significantly higher than in the control group. The immune responses induced by the bivalent OMV vaccine demonstrated the induction of bactericidal antibodies against the vaccine-homologous/PorA-related strains but also against heterologous strains, indicating the presence of protective antigens in OMVs and confirming the potential of clinical cross-protection.
authors.affiliation: GlaxoSmithKline Biologicals, rue de l'Institut 89, 1330 Rixensart, Belgium. dominique.boutriau@gskbio.com
authors.forename: Dominique
authors.initials: D
authors.lastname: Boutriau
authors.forename: Jan
authors.initials: J
authors.lastname: Poolman
authors.forename: Ray
authors.initials: R
authors.lastname: Borrow
authors.forename: Jamie
authors.initials: J
authors.lastname: Findlow
authors.forename: Javier Diez
authors.initials: JD
authors.lastname: Domingo
authors.forename: Joan
authors.initials: J
authors.lastname: Puig-Barbera
authors.forename: José María
authors.initials: JM
authors.lastname: Baldó
authors.forename: Victoria
authors.initials: V
authors.lastname: Planelles
authors.forename: Angels
authors.initials: A
authors.lastname: Jubert
authors.forename: Julia
authors.initials: J
authors.lastname: Colomer
authors.forename: Angel
authors.initials: A
authors.lastname: Gil
authors.forename: Karin
authors.initials: K
authors.lastname: Levie
authors.forename: Anne-Diane
authors.initials: AD
authors.lastname: Kervyn
authors.forename: Vincent
authors.initials: V
authors.lastname: Weynants
authors.forename: Francisco
authors.initials: F
authors.lastname: Dominguez
authors.forename: Ramon
authors.initials: R
authors.lastname: Barberá
authors.forename: Franklin
authors.initials: F
authors.lastname: Sotolongo
mesh_terms: D000293:Adolescent; D000907:Antibodies, Bacterial / Q000276:immunology*; D001425:Bacterial Outer Membrane Proteins / Q000276:immunology; D004306:Dose-Response Relationship, Immunologic; D006801:Humans; D007114:Immunization; D008589:Meningococcal Infections / Q000276:immunology / Q000517:prevention & control*; D022401:Meningococcal Vaccines / Q000008:administration & dosage / Q000276:immunology*; D009345:Neisseria meningitidis / Q000276:immunology*; D018272:Porins / Q000276:immunology*; D012449:Safety; D014614:Vaccines, Synthetic
chemical_list: D000907:Antibodies, Bacterial; D001425:Bacterial Outer Membrane Proteins; D022401:Meningococcal Vaccines; D018272:Porins; D014614:Vaccines, Synthetic