title: Robust and Balanced Immune Responses to All 4 Dengue Virus Serotypes Following Administration of a Single Dose of a Live Attenuated Tetravalent Dengue Vaccine to Healthy, Flavivirus-Naive Adults.
abstract: BACKGROUND
  The 4 serotypes of dengue virus, DENV-1-4, are the leading cause of arboviral disease globally. The ideal dengue vaccine would provide protection against all serotypes after a single dose.
  
  
  METHODS
  Two randomized, placebo-controlled trials were performed with 168 flavivirus-naive adults to demonstrate the safety and immunogenicity of a live attenuated tetravalent dengue vaccine (TV003), compared with those of a second tetravalent vaccine with an enhanced DENV-2 component (TV005), and to evaluate the benefit of a booster dose at 6 months. Safety data, viremia, and neutralizing antibody titers were evaluated.
  
  
  RESULTS
  A single dose of TV005 elicited a tetravalent response in 90% of vaccinees by 3 months after vaccination and a trivalent response in 98%. Compared with TV003, the higher-dose DENV-2 component increased the observed frequency of immunogenicity to DENV-2 in the TV005 trial. Both the first and second doses were well tolerated. Neither vaccine viremia, rash, nor a significant antibody boost were observed following a second dose.
  
  
  CONCLUSIONS
  A single subcutaneous dose of TV005 dengue vaccine is safe and induces a tetravalent antibody response at an unprecedented frequency among vaccinees. A second dose has limited benefit and appears to be unnecessary. Studies to confirm these findings and assess vaccine efficacy will now move to populations in regions where DENV transmission is endemic.
  
  
  BACKGROUND
  NCT01072786 and NCT01436422.
authors: Department of Medicine, Vaccine Testing Center, University of Vermont College of Medicine, Burlington.
authors: Beth D
authors: BD
authors: Kirkpatrick
authors: Center for Immunization Research, Johns Hopkins University School of Public Health, Baltimore.
authors: Anna P
authors: AP
authors: Durbin
authors: Department of Medicine, Vaccine Testing Center, University of Vermont College of Medicine, Burlington.
authors: Kristen K
authors: KK
authors: Pierce
authors: Department of Medicine, Vaccine Testing Center, University of Vermont College of Medicine, Burlington.
authors: Marya P
authors: MP
authors: Carmolli
authors: Center for Immunization Research, Johns Hopkins University School of Public Health, Baltimore.
authors: Cecilia M
authors: CM
authors: Tibery
authors: Center for Immunization Research, Johns Hopkins University School of Public Health, Baltimore.
authors: Palmtama L
authors: PL
authors: Grier
authors: Center for Immunization Research, Johns Hopkins University School of Public Health, Baltimore.
authors: Noreen
authors: N
authors: Hynes
authors: Department of Medicine, Vaccine Testing Center, University of Vermont College of Medicine, Burlington.
authors: Sean A
authors: SA
authors: Diehl
authors: Center for Immunization Research, Johns Hopkins University School of Public Health, Baltimore.
authors: Dan
authors: D
authors: Elwood
authors: Department of Medicine, Vaccine Testing Center, University of Vermont College of Medicine, Burlington.
authors: Adrienne P
authors: AP
authors: Jarvis
authors: Center for Immunization Research, Johns Hopkins University School of Public Health, Baltimore.
authors: Beulah P
authors: BP
authors: Sabundayo
authors: Department of Medicine, Vaccine Testing Center, University of Vermont College of Medicine, Burlington.
authors: Caroline E
authors: CE
authors: Lyon
authors: Department of Medicine, Vaccine Testing Center, University of Vermont College of Medicine, Burlington.
authors: Catherine J
authors: CJ
authors: Larsson
authors: Center for Immunization Research, Johns Hopkins University School of Public Health, Baltimore.
authors: Matthew
authors: M
authors: Jo
authors: Center for Immunization Research, Johns Hopkins University School of Public Health, Baltimore.
authors: Janece M
authors: JM
authors: Lovchik
authors: National Institutes of Allergy and Infectious Diseases, Bethesda, Maryland.
authors: Catherine J
authors: CJ
authors: Luke
authors: Department of Medicine, Vaccine Testing Center, University of Vermont College of Medicine, Burlington.
authors: Mary C
authors: MC
authors: Walsh
authors: Department of Medicine, Vaccine Testing Center, University of Vermont College of Medicine, Burlington.
authors: Ellen A
authors: EA
authors: Fraser
authors: National Institutes of Allergy and Infectious Diseases, Bethesda, Maryland.
authors: Kanta
authors: K
authors: Subbarao
authors: National Institutes of Allergy and Infectious Diseases, Bethesda, Maryland.
authors: Steven S
authors: SS
authors: Whitehead
mesh_terms: D000293:Adolescent; D000328:Adult; D057134:Antibodies, Neutralizing / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood; D053059:Dengue Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*; D003716:Dengue Virus / Q000276:immunology*; D064420:Drug-Related Side Effects and Adverse Reactions; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D007279:Injections, Subcutaneous; D008297:Male; D008875:Middle Aged; D010919:Placebos / Q000008:administration & dosage; D014611:Vaccination / Q000379:methods*; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D014766:Viremia; D055815:Young Adult
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D053059:Dengue Vaccines; D010919:Placebos; D014613:Vaccines, Attenuated
keywords: clinical trial; dengue vaccine; live attenuated tetravalent vaccine