title: Persistence of bactericidal antibodies following booster vaccination with 4CMenB at 12, 18 or 24months and immunogenicity of a fifth dose administered at 4years of age-a phase 3 extension to a randomised controlled trial.
abstract: 4CMenB is immunogenic in infants and toddlers. We assessed persistence of human complement serum bactericidal activity (hSBA) following a fourth dose administered at 12, 18 or 24months and characterised the antibody response to a fifth dose administered at 4years of age.
  
  
  
  A phase 3, open label, multi-centre extension to a randomised controlled trial conducted in four countries (number of centres): Czech Republic (nineteen), Italy (four), Spain (four) and the United Kingdom (four). Four-year-old children who were either 4CMenB-naïve or had previously received a variety of 3-dose infant priming schedules and a booster vaccine as toddlers (follow-on group) were recruited. Venous blood samples were obtained to determine hSBA against four reference strains; acting as targets to assess immunity to each of the vaccine antigens, NadA (5/99), fHbp (H44/76), PorA (NZ98/254), and NHBA (M10713) at baseline (prior to vaccination, all participants) and one month following a dose of 4CMenB for all vaccine-naïve and follow-on participants primed with the 2, 3, 4 schedule, and a third of follow-on participants primed with a 2, 4, 6month schedule.
  
  
  
  At baseline (prior to vaccination), the proportion of participants (n=468) with hSBA titers⩾5 was similar across all followon groups: 89-100% against 5/99; 12-35% for H44/76; 8-12% for NZ98/254 and 53-80% for M10713 compared with 5%, 0%, 0%; and 60% respectively, for the vaccine-naïve controls (n=206). Following a dose of 4CMenB at 4years of age, this increased to 100% (5/99), 97-100% (H44/76), 80-95 % (NZ98/254) and 84-100% (M10713) (n=210), compared with 89%, 70%, 24%, and 76% respectively for vaccine-naïve controls (n=192).
  
  
  
  Waning of protective antibodies occurred 24–36 months after toddler booster regardless of age at boost. This was least marked against target strains 5/99 and M10713. A robust memory response occurred after a booster dose given at 4 years of age.
authors.affiliation: Oxford Vaccine Group, Department of Paediatrics, University of Oxford and the NIHR Oxford Biomedical Research Centre, Oxford, UK. Electronic address: mildred.iro@paediatrics.ox.ac.uk.
authors.forename: Mildred A
authors.initials: MA
authors.lastname: Iro
authors.affiliation: Oxford Vaccine Group, Department of Paediatrics, University of Oxford and the NIHR Oxford Biomedical Research Centre, Oxford, UK.
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Snape
authors.affiliation: Oxford Vaccine Group, Department of Paediatrics, University of Oxford and the NIHR Oxford Biomedical Research Centre, Oxford, UK; Nuffield Department of Primary Health Care Health Sciences, University of Oxford, Oxford, UK.
authors.forename: Merryn
authors.initials: M
authors.lastname: Voysey
authors.affiliation: Nuffield Department of Primary Health Care Health Sciences, University of Oxford, Oxford, UK.
authors.forename: Sena
authors.initials: S
authors.lastname: Jawad
authors.affiliation: Bristol Children's Vaccine Centre, University of Bristol, Bristol, UK.
authors.forename: Adam
authors.initials: A
authors.lastname: Finn
authors.affiliation: St Georges Vaccine Institute, St George's, University of London, London, UK.
authors.forename: Paul T
authors.initials: PT
authors.lastname: Heath
authors.affiliation: Azienda Ospedaliero-Universitaria Maggiore della Carità, Clinica Pediatrica, Novara, Italy.
authors.forename: Gianni
authors.initials: G
authors.lastname: Bona
authors.affiliation: Pediatric Highly Intensive Care Unit, Università degli Studi di Milano, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
authors.forename: Susanna
authors.initials: S
authors.lastname: Esposito
authors.affiliation: Vaccine Research Area, Fundación para el Fomento de la Investigación Sanitaria y Biomédica (FISABIO), Valencia, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Diez-Domingo
authors.affiliation: Charles University Prague, School of Medicine Hradec Kralove, Czech Republic.
authors.forename: Roman
authors.initials: R
authors.lastname: Prymula
authors.affiliation: Novartis Vaccines and Diagnostics Inc., Cambridge, MA, USA.
authors.forename: Adefowope
authors.initials: A
authors.lastname: Odueyungbo
authors.affiliation: GSK Vaccines S.r.l., Siena, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Toneatto
authors.affiliation: Novartis Vaccines and Diagnostics Inc., Cambridge, MA, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Dull
authors.affiliation: Oxford Vaccine Group, Department of Paediatrics, University of Oxford and the NIHR Oxford Biomedical Research Centre, Oxford, UK.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Pollard
mesh_terms: D000907:Antibodies, Bacterial / Q000097:blood*; D000917:Antibody Formation; D000942:Antigens, Bacterial / Q000276:immunology; D001770:Blood Bactericidal Activity; D002675:Child, Preschool; D003165:Complement System Proteins / Q000276:immunology; D018153:Czech Republic; D005260:Female; D006801:Humans; D007117:Immunization, Secondary; D007223:Infant; D007558:Italy; D008297:Male; D022401:Meningococcal Vaccines / Q000008:administration & dosage* / Q000276:immunology*; D013030:Spain; D013997:Time Factors; D006113:United Kingdom
chemical_list: C570015:4CMenB vaccine; D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D022401:Meningococcal Vaccines; D003165:Complement System Proteins
keywords: 4CMenB; MenW; Neisseria meningitidis; Reactogenicity; Toddler; Vaccine