title: Non-inferiority of mammalian cell-derived quadrivalent subunit influenza virus vaccines compared to trivalent subunit influenza virus vaccines in healthy children: a phase III randomized, multicenter, double-blind clinical trial.
abstract: OBJECTIVE
  The safety and immunogenicity of mammalian cell-derived quadrivalent influenza vaccine (QIVc) as compared with trivalent influenza vaccines (TIV1c/TIV2c) was evaluated in children aged ≥4 to <18 years.
  
  
  METHODS
  Two thousand three hundred and thirty-three subjects were randomized 2:1:1 to receive either one or two doses of study vaccine depending on previous vaccination status. Hemagglutination inhibition antibody responses for all four influenza strains were performed 3 weeks after the last dose. Reactogenicity and safety were also assessed (ClinicalTrials.gov: NCT01992107).
  
  
  RESULTS
  QIVc met the non-inferiority criteria against all four vaccine strains and demonstrated superiority for both influenza B strains over the unmatched B lineage included in the comparator vaccines, when geometric mean titers and seroconversion rates were compared at 3 weeks after the last vaccination. Similar percentages of subjects experienced solicited and unsolicited adverse events (AEs) across all subgroups. Unsolicited AEs, serious AEs, medically attended AEs, and new onset chronic disease were reported in comparable percentages of subjects in all study groups. No vaccine-related serious AEs or deaths occurred.
  
  
  CONCLUSIONS
  QIVc demonstrated a similar safety profile and immunogenicity responses against all four vaccine strains without signs of immune interference on addition of an alternate lineage B strain compared with TIV1c/TIV2c and may provide broader protection against both influenza B lineages in children.
authors.affiliation: Heartland Research Associates, LLC, Newton, Kansas, USA.
authors.forename: Robyn
authors.initials: R
authors.lastname: Hartvickson
authors.affiliation: Premier Health Research Center, LLC, Downey, California, USA.
authors.forename: Marilou
authors.initials: M
authors.lastname: Cruz
authors.affiliation: The Center for Pharmaceutical Research, Kansas City, Missouri, USA.
authors.forename: John
authors.initials: J
authors.lastname: Ervin
authors.affiliation: California Research Foundation, San Diego, California, USA.
authors.forename: Donald
authors.initials: D
authors.lastname: Brandon
authors.affiliation: Novartis Vaccines and Diagnostics Inc., Cambridge, Massachusetts, USA.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Forleo-Neto
authors.affiliation: Novartis Vaccines and Diagnostics Inc., Cambridge, Massachusetts, USA.
authors.forename: Alemnew F
authors.initials: AF
authors.lastname: Dagnew
authors.affiliation: Novartis Vaccines and Diagnostics Inc., Cambridge, Massachusetts, USA.
authors.forename: Richa
authors.initials: R
authors.lastname: Chandra
authors.affiliation: Novartis Vaccines and Diagnostics Inc., Cambridge, Massachusetts, USA.
authors.forename: Kelly
authors.initials: K
authors.lastname: Lindert
authors.affiliation: Novartis Pharmaceuticals Canada Inc., 385 Bouchard Blvd, Dorval, Quebec, H9S 1A9, Canada. Electronic address: ahmed.abdul_mateen@novartis.com.
authors.forename: Ahmed Abdul
authors.initials: AA
authors.lastname: Mateen
mesh_terms: D000293:Adolescent; D000914:Antibodies, Viral / Q000097:blood; D000917:Antibody Formation; D002648:Child; D002675:Child, Preschool; D004311:Double-Blind Method; D005260:Female; D006385:Hemagglutination Inhibition Tests; D006801:Humans; D007252:Influenza Vaccines / Q000276:immunology*; D007251:Influenza, Human / Q000517:prevention & control*; D008297:Male; D000069078:Seroconversion; D014611:Vaccination; D015164:Vaccines, Inactivated / Q000276:immunology
chemical_list: D000914:Antibodies, Viral; D007252:Influenza Vaccines; D015164:Vaccines, Inactivated
keywords: Influenza; MDCK; Pediatric; Quadrivalent; Trivalent; Vaccine