title: Safety and Immunogenicity of a Live Attenuated Tetravalent Dengue Vaccine Candidate in Flavivirus-Naive Adults: A Randomized, Double-Blinded Phase 1 Clinical Trial.
abstract: BACKGROUND
  Dengue viruses (DENVs) infect >300 million people annually, causing 96 million cases of dengue disease and 22 000 deaths [1]. A safe vaccine that protects against DENV disease is a global health priority [2].
  
  
  METHODS
  We enrolled 72 flavivirus-naive healthy adults in a phase 1 double-blinded, randomized, placebo-controlled dose-escalation trial (low and high dose) of a live attenuated recombinant tetravalent dengue vaccine candidate (TDV) given in 2 doses 90 days apart. Volunteers were followed for safety, vaccine component viremia, and development of neutralizing antibodies to the 4 DENV serotypes.
  
  
  RESULTS
  The majority of adverse events were mild, with no vaccine-related serious adverse events. Vaccinees reported injection site pain (52% vs 17%) and erythema (73% vs 25%) more frequently than placebo recipients. Low levels of TDV-serotype 2 (TDV-2), TDV-3, and TDV-4 viremia were observed after the first but not second administration of vaccine. Overall seroconversion rates and geometric mean neutralization titers after 2 doses were 84.2% and 54.1, respectively, for DENV serotype 1 (DENV-1); 92.1% and 292.8, respectively, for DENV-2; 86.8% and 32.3, respectively, for DENV-3; and 71.1% and 15.0, respectively, for DENV-4. More than 90.0% of high-dose recipients had trivalent or broader responses.
  
  
  CONCLUSIONS
  TDV was generally well tolerated, induced trivalent or broader neutralizing antibodies to DENV in most flavivirus-naive vaccinees, and is undergoing further development.
  
  
  BACKGROUND
  NCT01110551.
authors: Department of Internal Medicine, Division of Infectious Diseases, Allergy and Immunology, Saint Louis University School of Medicine St. Louis Veterans Administration Medical Center, Missouri.
authors: Sarah L
authors: SL
authors: George
authors: EMMES Corporation, Rockville, Maryland.
authors: Mimi A
authors: MA
authors: Wong
authors: EMMES Corporation, Rockville, Maryland.
authors: Tina J T
authors: TJ
authors: Dube
authors: Arboviral Diseases Branch, Division of Vector-Borne Disease, Centers for Disease Control and Prevention, Fort Collins, Colorado.
authors: Karen L
authors: KL
authors: Boroughs
authors: Arboviral Diseases Branch, Division of Vector-Borne Disease, Centers for Disease Control and Prevention, Fort Collins, Colorado.
authors: Janae L
authors: JL
authors: Stovall
authors: Arboviral Diseases Branch, Division of Vector-Borne Disease, Centers for Disease Control and Prevention, Fort Collins, Colorado.
authors: Betty E
authors: BE
authors: Luy
authors: Arboviral Diseases Branch, Division of Vector-Borne Disease, Centers for Disease Control and Prevention, Fort Collins, Colorado.
authors: Aurelia A
authors: AA
authors: Haller
authors: Takeda Vaccines, Deerfield, Illinois.
authors: Jorge E
authors: JE
authors: Osorio
authors: Department of Internal Medicine, Division of Infectious Diseases, Allergy and Immunology, Saint Louis University School of Medicine.
authors: Linda M
authors: LM
authors: Eggemeyer
authors: Department of Internal Medicine, Division of Infectious Diseases, Allergy and Immunology, Saint Louis University School of Medicine.
authors: Sharon
authors: S
authors: Irby-Moore
authors: Department of Internal Medicine, Division of Infectious Diseases, Allergy and Immunology, Saint Louis University School of Medicine.
authors: Sharon E
authors: SE
authors: Frey
authors: Arboviral Diseases Branch, Division of Vector-Borne Disease, Centers for Disease Control and Prevention, Fort Collins, Colorado.
authors: Claire Y-H
authors: CY
authors: Huang
authors: Takeda Vaccines, Deerfield, Illinois.
authors: Dan T
authors: DT
authors: Stinchcomb
mesh_terms: D000293:Adolescent; D000328:Adult; D057134:Antibodies, Neutralizing / Q000276:immunology; D003715:Dengue / Q000276:immunology / Q000517:prevention & control*; D053059:Dengue Vaccines / Q000276:immunology*; D003716:Dengue Virus / Q000276:immunology*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D012449:Safety; D014611:Vaccination; D014613:Vaccines, Attenuated / Q000276:immunology; D014766:Viremia; D055815:Young Adult
chemical_list: D057134:Antibodies, Neutralizing; D053059:Dengue Vaccines; D014613:Vaccines, Attenuated
keywords: Dengue vaccine; clinical trial; live attenuated tetravalent; neutralizing antibody; viremia