title: Protective efficacy of the recombinant, live-attenuated, CYD tetravalent dengue vaccine in Thai schoolchildren: a randomised, controlled phase 2b trial.
abstract: BACKGROUND
  Roughly half the world's population live in dengue-endemic countries, but no vaccine is licensed. We investigated the efficacy of a recombinant, live, attenuated tetravalent dengue vaccine.
  
  
  METHODS
  In this observer-masked, randomised, controlled, monocentre, phase 2b, proof-of-concept trial, healthy Thai schoolchildren aged 4-11 years were randomly assigned (2:1) to receive three injections of dengue vaccine or control (rabies vaccine or placebo) at months 0, 6, and 12. Randomisation was by computer-generated permuted blocks of six and participants were assigned with an interactive response system. Participants were actively followed up until month 25. All acute febrile illnesses were investigated. Dengue viraemia was confirmed by serotype-specific RT-PCR and non-structural protein 1 ELISA. The primary objective was to assess protective efficacy against virologically confirmed, symptomatic dengue, irrespective of severity or serotype, occurring 1 month or longer after the third injection (per-protocol analysis). This trial is registered at ClinicalTrials.gov, NCT00842530.
  
  
  RESULTS
  4002 participants were assigned to vaccine (n=2669) or control (n=1333). 3673 were included in the primary analysis (2452 vaccine, 1221 control). 134 cases of virologically confirmed dengue occurred during the study. Efficacy was 30·2% (95% CI -13·4 to 56·6), and differed by serotype. Dengue vaccine was well tolerated, with no safety signals after 2 years of follow-up after the first dose.
  
  
  CONCLUSIONS
  These data show for the first time that a safe vaccine against dengue is possible. Ongoing large-scale phase 3 studies in various epidemiological settings will provide pivotal data for the CYD dengue vaccine candidate.
  
  
  BACKGROUND
  Sanofi Pasteur.
authors.affiliation: Department of Tropical Pediatrics, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
authors.forename: Arunee
authors.initials: A
authors.lastname: Sabchareon
authors.forename: Derek
authors.initials: D
authors.lastname: Wallace
authors.forename: Chukiat
authors.initials: C
authors.lastname: Sirivichayakul
authors.forename: Kriengsak
authors.initials: K
authors.lastname: Limkittikul
authors.forename: Pornthep
authors.initials: P
authors.lastname: Chanthavanich
authors.forename: Saravudh
authors.initials: S
authors.lastname: Suvannadabba
authors.forename: Vithaya
authors.initials: V
authors.lastname: Jiwariyavej
authors.forename: Wut
authors.initials: W
authors.lastname: Dulyachai
authors.forename: Krisana
authors.initials: K
authors.lastname: Pengsaa
authors.forename: T Anh
authors.initials: TA
authors.lastname: Wartel
authors.forename: Annick
authors.initials: A
authors.lastname: Moureau
authors.forename: Melanie
authors.initials: M
authors.lastname: Saville
authors.forename: Alain
authors.initials: A
authors.lastname: Bouckenooghe
authors.forename: Simonetta
authors.initials: S
authors.lastname: Viviani
authors.forename: Nadia G
authors.initials: NG
authors.lastname: Tornieporth
authors.forename: Jean
authors.initials: J
authors.lastname: Lang
mesh_terms: D002648:Child; D002675:Child, Preschool; D003715:Dengue / Q000517:prevention & control*; D053059:Dengue Vaccines / Q000276:immunology / Q000627:therapeutic use*; D003716:Dengue Virus / Q000276:immunology; D005260:Female; D006801:Humans; D008297:Male; D012703:Serotyping; D016896:Treatment Outcome; D014613:Vaccines, Attenuated; D014614:Vaccines, Synthetic
chemical_list: D053059:Dengue Vaccines; D014613:Vaccines, Attenuated; D014614:Vaccines, Synthetic