title: Safety and Immunogenicity of a Tetravalent Dengue Vaccine Candidate in Healthy Children and Adults in Dengue-Endemic Regions: A Randomized, Placebo-Controlled Phase 2 Study.
abstract: BACKGROUND
  A safe, effective tetravalent dengue vaccine is a global health priority. The safety and immunogenicity of a live attenuated, recombinant tetravalent dengue vaccine candidate (TDV) were evaluated in healthy volunteers from dengue-endemic countries.
  
  
  METHODS
  This multicenter, double-blind, phase 2 study was conducted in Puerto Rico, Colombia, Singapore, and Thailand. During stage I, 148 volunteers aged 1.5-45 years were sequentially enrolled into 4 age-descending groups and randomized at a ratio of 2:1 to receive TDV or placebo. In stage II (group 5), 212 children aged 1.5-11 years were randomized at a ratio of 3:1 to receive TDV or placebo. Participants received a subcutaneous injection of TDV or placebo on days 0 and 90 and were followed for analysis of safety, seropositivity, and neutralizing antibodies to DENV-1-4.
  
  
  RESULTS
  Injection site pain, itching, and erythema (mostly mild) were the only solicited adverse events more frequently reported with TDV than with placebo in all age groups. After 2 TDV doses, seropositivity was >95% in all 5 groups for DENV-1-3 and 72.7%-100% for DENV-4; geometric mean titers ranged from 582 to 1187 for DENV-1, from 582 to 1187 for DENV-2, from 196 to 630 for DENV-3, and from 41 to 210 for DENV-4 among the 5 groups.
  
  
  CONCLUSIONS
  TDV was well tolerated and immunogenic in volunteers aged 1.5-45 years, irrespective of prevaccination dengue exposure.
authors.affiliation: Department of Tropical Pediatrics, Faculty of Tropical Medicine, Mahidol University.
authors.forename: Chukiat
authors.initials: C
authors.lastname: Sirivichayakul
authors.affiliation: CAIMED Center, Ponce School of Medicine.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Barranco-Santana
authors.affiliation: Department of Pediatrics.
authors.forename: Inés
authors.initials: I
authors.lastname: Esquilin-Rivera
authors.affiliation: Division of Infectious Disease, Changi General Hospital.
authors.forename: Helen M L
authors.initials: HM
authors.lastname: Oh
authors.affiliation: Takeda Vaccines, Inc., Deerfield, Illinois.
authors.forename: Marsha
authors.initials: M
authors.lastname: Raanan
authors.affiliation: Department of Microbiology and Medical Zoology Department of Internal Medicine, University of Puerto Rico School of Medicine Latin Clinical Trial Center, San Juan, Puerto Rico.
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Sariol
authors.affiliation: Department of Paediatrics, National University of Singapore.
authors.forename: Lynette P
authors.initials: LP
authors.lastname: Shek
authors.affiliation: Pediatric Department, Phramongkutklao Hospital, Bangkok, Thailand.
authors.forename: Sriluck
authors.initials: S
authors.lastname: Simasathien
authors.affiliation: Takeda Vaccines, Inc., Deerfield, Illinois.
authors.forename: Mary Kathryn
authors.initials: MK
authors.lastname: Smith
authors.affiliation: Program for the Study and Control of Tropical Diseases, Universidad de Antioquia, Medellín, Colombia.
authors.forename: Ivan Dario
authors.initials: ID
authors.lastname: Velez
authors.affiliation: Takeda Vaccines Pte. Ltd., Singapore.
authors.forename: Derek
authors.initials: D
authors.lastname: Wallace
authors.affiliation: Orra Group, Boulder, Colorado.
authors.forename: Gilad S
authors.initials: GS
authors.lastname: Gordon
authors.affiliation: Takeda Vaccines, Inc., Deerfield, Illinois.
authors.forename: Dan T
authors.initials: DT
authors.lastname: Stinchcomb
mesh_terms: D000293:Adolescent; D000328:Adult; D057134:Antibodies, Neutralizing / Q000276:immunology; D000914:Antibodies, Viral / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D003105:Colombia; D003715:Dengue / Q000276:immunology / Q000517:prevention & control*; D053059:Dengue Vaccines / Q000008:administration & dosage / Q000276:immunology* / Q000592:standards; D003716:Dengue Virus / Q000276:immunology*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007223:Infant; D007279:Injections, Subcutaneous; D008297:Male; D008875:Middle Aged; D011647:Puerto Rico; D012449:Safety; D012846:Singapore; D013785:Thailand; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000276:immunology / Q000592:standards; D055815:Young Adult
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D053059:Dengue Vaccines; D014613:Vaccines, Attenuated
keywords: adults; children; immunogenicity; live attenuated tetravalent dengue vaccine; safety