title: Immune responses to a recombinant, four-component, meningococcal serogroup B vaccine (4CMenB) in adolescents: a phase III, randomized, multicentre, lot-to-lot consistency study.
abstract: BACKGROUND
  For decades, a broadly effective vaccine against serogroup B Neisseria meningitidis (MenB) has remained elusive. Recently, a four-component recombinant vaccine (4CMenB) has been developed and is now approved in Europe, Canada, Australia and some Latin American countries. This phase III, randomized study evaluated the lot consistency, early immune responses and the safety profile of 4CMenB in 11 to 17-year-old adolescents in Australia and Canada (NCT01423084).
  
  
  METHODS
  In total, 344 adolescents received two doses of one of 2 lots of 4CMenB, 1-month apart. Immunogenicity was assessed before, 2-weeks and 1-month following the second vaccination. Serum bactericidal activity using human complement (hSBA) was measured against three reference strains 44/76-SL, 5/99 and NZ98/254, selected to express one of the vaccine antigens; Neisseria adhesin A (NadA), factor H binding protein (fHbp) and porin A (PorA) containing outer membrane vesicle (OMV), respectively. Responses to the Neisseria heparin binding antigen (NHBA) were assessed with enzyme linked immunosorbent assay (ELISA). Local and systemic reactions were recorded for 7 days following each vaccination; unsolicited adverse events were monitored throughout the study.
  
  
  RESULTS
  Immunological equivalence of the two lots of 4CMenB was established at 1-month. At baseline, ≤7% of participants had hSBA titers ≥5 to all three reference strains. Two weeks following the second dose of 4CMenB, all participants had hSBA titers ≥5 against fHbp and NadA compared with 84-96% against the PorA reference strains. At 1-month, corresponding proportions were 99%, 100% and 70-79%, respectively. Both lots were generally well tolerated and had similar adverse event profiles.
  
  
  CONCLUSIONS
  Two doses of 4CMenB had an acceptable safety profile and induced a robust immune response in adolescents. Peak antibody responses were observed at 14 days following vaccination. While a substantial non-uniform antigen-dependent early decline in antibody titers was seen thereafter, a significant percentage of participants continued to maintain protective hSBA titers at 1-month.
authors.affiliation: Vaccine and Immunisation Research Group (VIRGo), Murdoch Childrens Research Institute and Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Australia.
authors.forename: Kirsten P
authors.initials: KP
authors.lastname: Perrett
authors.affiliation: Vaccine and Immunisation Research Group (VIRGo), Murdoch Childrens Research Institute and Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Australia.
authors.forename: Jodie
authors.initials: J
authors.lastname: McVernon
authors.affiliation: School of Paediatrics and Child Health, University of Western Australia, Wesfarmers Centre of Vaccines and Infectious Diseases, Telethon Kids Institute, Princess Margaret Hospital for Children, Perth, Australia.
authors.forename: Peter C
authors.initials: PC
authors.lastname: Richmond
authors.affiliation: Vaccinology and Immunology Research Trials Unit (VIRTU), Women's and Children's Hospital, School of Paediatrics and Reproductive Health and Robinson Research Institute, The University of Adelaide, Adelaide, Australia.
authors.forename: Helen
authors.initials: H
authors.lastname: Marshall
authors.affiliation: Queensland Paediatric Infectious Diseases Laboratory (Qpid), Queensland Children's Medical Research Institute, Royal Children's Hospital, University of Queensland, Brisbane, Australia.
authors.forename: Michael
authors.initials: M
authors.lastname: Nissen
authors.affiliation: Novartis Vaccines and Diagnostics Inc., Cambridge, MA, USA.
authors.forename: Allison
authors.initials: A
authors.lastname: August
authors.affiliation: Novartis Vaccines and Diagnostics Inc., Cambridge, MA, USA.
authors.forename: Sandra
authors.initials: S
authors.lastname: Percell
authors.affiliation: Novartis Vaccines and Diagnostics S.r.l., Siena, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Toneatto
authors.affiliation: Vaccine and Immunisation Research Group (VIRGo), Murdoch Childrens Research Institute and Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Australia. Electronic address: t.nolan@unimelb.edu.au.
authors.forename: Terry
authors.initials: T
authors.lastname: Nolan
mesh_terms: D000293:Adolescent; D000907:Antibodies, Bacterial / Q000097:blood; D000942:Antigens, Bacterial / Q000276:immunology; D001315:Australia; D001770:Blood Bactericidal Activity; D002170:Canada; D002648:Child; D003165:Complement System Proteins; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007115:Immunization Schedule; D008297:Male; D008589:Meningococcal Infections / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control*; D022401:Meningococcal Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*; D038541:Neisseria meningitidis, Serogroup B / Q000276:immunology*; D016896:Treatment Outcome
chemical_list: C570015:4CMenB vaccine; D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D022401:Meningococcal Vaccines; D003165:Complement System Proteins
keywords: Adolescence; Immunity; Immunization; Neisseria meningitidis; Serogroup B meningococcal vaccine