title: 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].
authors.affiliation: a Infectious Disease Department; Hospital del Niño ; Panama City , Panama.
authors.forename: Xavier
authors.initials: X
authors.lastname: Saez-Llorens
authors.forename: Diana Catalina
authors.initials: DC
authors.lastname: Aguilera Vaca
authors.forename: Katia
authors.initials: K
authors.lastname: Abarca
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Maho
authors.forename: Maria Gabriela
authors.initials: MG
authors.lastname: Graña
authors.forename: Esther
authors.initials: E
authors.lastname: Heijnen
authors.forename: Igor
authors.initials: I
authors.lastname: Smolenov
authors.forename: Peter M
authors.initials: PM
authors.lastname: Dull
mesh_terms: D000293:Adolescent; D001770:Blood Bactericidal Activity; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology / Q000473:pathology; D015507:Drugs, Investigational / Q000008:administration & dosage / Q000009:adverse effects*; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D008297:Male; D022401:Meningococcal Vaccines / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology*; D010919:Placebos / Q000008:administration & dosage; D017778:Vaccines, Combined / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology
chemical_list: D015507:Drugs, Investigational; D022401:Meningococcal Vaccines; D010919:Placebos; D017778:Vaccines, Combined
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