title: Safety and tolerability of a cell culture derived trivalent subunit inactivated influenza vaccine administered to healthy children and adolescents: A Phase III, randomized, multicenter, observer-blind study.
abstract: BACKGROUND
  Cell culture-derived inactivated influenza vaccines (TIVc) are necessary for scale and predictability of production to meet global demand. This study compared the safety and tolerability of TIVc with an egg-derived trivalent influenza vaccine (TIVf) in 4-17 yearolds.
  
  
  METHODS
  A Phase 3 observer blind, multicenter study enrolled 2055 healthy participants randomized 2:1 to receive either TIVc or TIVf, respectively (1372 TIVc and 683 TIVf evaluable subjects). Participants received one dose each on Days 1 and 28 (4-8 year-olds not previously vaccinated [NPV]) or one dose on Day 1 (4-8 and 9-17 yearolds previously vaccinated [PV]). Solicited adverse events (AEs) occurring within 7 days after each vaccination were assessed; participants were followed up for 6 months after their last dose for safety.
  
  
  RESULTS
  Most solicited and unsolicited AEs were mild to moderate with <1% in the severe category. No withdrawals due to AEs, deaths or vaccine-related SAEs were reported. TIVc and TIVf were similar in percentages of participants reporting solicited reactions in 4-8 years NPV group after the 1st dose: local reactions, TIVc: 48%, TIVf: 43%; systemic reactions, TIVc: 34%, TIVf: 32%; percentages were lower following the 2nd dose in TIVc; local reactions: TIVc: 40%; TIVf: 43%; systemic reactions: TIVc: 21%; TIVf: 22%. In 4-17 years PV group, solicited reactions were lower following TIVf, local reactions: TIVc: 53%; TIVf: 43%; systemic reactions: TIVc: 37%, TIVf: 30%. Injection-site pain was the most common solicited reaction, and was similar following TIVc and TIVf in 4-8 yearolds (TIVc: 56%; TIVf: 55%), and lower following TIVf in 9-17 years group (TIVc: 52%; TIVf: 42%). Reporting of unsolicited AEs was similar for TIVc and TIVf across the two age groups.
  
  
  CONCLUSIONS
  TIVc was well tolerated and had a safety and reactogenicity profile similar to that of TIVf in healthy 4-17 yearolds (NCT01857206).
authors.affiliation: The Melbourne School of Population and Global Health and Murdoch Childrens Research Institute, University of Melbourne, Melbourne, Australia.. Electronic address: t.nolan@unimelb.edu.au.
authors.forename: Terry
authors.initials: T
authors.lastname: Nolan
authors.affiliation: Queen Sirikit National Institute of Child Health, Bangkok, Thailand.
authors.forename: Tawee
authors.initials: T
authors.lastname: Chotpitayasunondh
authors.affiliation: Research Institute for Tropical Medicine, Muntinlupa City, Philippines.
authors.forename: Maria Rosario
authors.initials: MR
authors.lastname: Capeding
authors.affiliation: Southern Clinical Trials Ltd, Beckenham, Christchurch, New Zealand.
authors.forename: Simon
authors.initials: S
authors.lastname: Carson
authors.affiliation: Senders Pediatrics, Cleveland, OH, USA.
authors.forename: Shelly David
authors.initials: SD
authors.lastname: Senders
authors.affiliation: Novartis Vaccines and Diagnostics GmbH, Marburg, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Jaehnig
authors.affiliation: Novartis Pharma BV, Amsterdam, The Netherlands.
authors.forename: Richard
authors.initials: R
authors.lastname: de Rooij
authors.affiliation: Novartis Vaccines and Diagnostics Inc., Cambridge, MA, USA.
authors.forename: Richa
authors.initials: R
authors.lastname: Chandra
mesh_terms: D000293:Adolescent; D018929:Cell Culture Techniques; D002648:Child; D002675:Child, Preschool; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology* / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007252:Influenza Vaccines / Q000008:administration & dosage* / Q000009:adverse effects*; D008297:Male; D016037:Single-Blind Method; D013678:Technology, Pharmaceutical; D015164:Vaccines, Inactivated / Q000008:administration & dosage / Q000276:immunology; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000276:immunology; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000276:immunology
chemical_list: D007252:Influenza Vaccines; D015164:Vaccines, Inactivated; D022223:Vaccines, Subunit; D014614:Vaccines, Synthetic
keywords: Cell-culture; Children; Influenza; Safety