title: The live attenuated dengue vaccine TV003 elicits complete protection against dengue in a human challenge model.
abstract: A dengue human challenge model can be an important tool to identify candidate dengue vaccines that should be further evaluated in large efficacy trials in endemic areas. Dengue is responsible for about 390 million infections annually. Protective efficacy results for the most advanced dengue vaccine candidate (CYD) were disappointing despite its ability to induce neutralizing antibodies against all four dengue virus (DENV) serotypes. TV003 is a live attenuated tetravalent DENV vaccine currently in phase 2 evaluation. To better assess the protective efficacy of TV003, a randomized double-blind, placebo-controlled trial in which recipients of TV003 or placebo were challenged 6 months later with a DENV-2 strain, rDEN2Δ30, was conducted. The primary endpoint of the trial was protection against dengue infection, defined as rDEN2Δ30 viremia. Secondary endpoints were protection against rash and neutropenia. All 21 recipients of TV003 who were challenged with rDEN2Δ30 were protected from infection with rDEN2Δ30. None developed viremia, rash, or neutropenia after challenge. In contrast, 100% of the 20 placebo recipients who were challenged with rDEN2Δ30 developed viremia, 80% developed rash, and 20% developed neutropenia. TV003 induced complete protection against challenge with rDEN2Δ30 administered 6 months after vaccination. TV003 will be further evaluated in dengue-endemic areas. The controlled dengue human challenge model can accelerate vaccine development by evaluating the protection afforded by the vaccine, thereby eliminating poor candidates from further consideration before the initiation of large efficacy trials.
authors.affiliation: Vaccine Testing Center, Department of Medicine, University of Vermont College of Medicine, Burlington, VT 05401, USA.
authors.forename: Beth D
authors.initials: BD
authors.lastname: Kirkpatrick
authors.affiliation: National Institutes of Allergy and Infectious Diseases, Bethesda, MD 20892, USA.
authors.forename: Stephen S
authors.initials: SS
authors.lastname: Whitehead
authors.affiliation: Vaccine Testing Center, Department of Medicine, University of Vermont College of Medicine, Burlington, VT 05401, USA.
authors.forename: Kristen K
authors.initials: KK
authors.lastname: Pierce
authors.affiliation: Center for Immunization Research, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA.
authors.forename: Cecilia M
authors.initials: CM
authors.lastname: Tibery
authors.affiliation: Center for Immunization Research, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA.
authors.forename: Palmtama L
authors.initials: PL
authors.lastname: Grier
authors.affiliation: Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors.forename: Noreen A
authors.initials: NA
authors.lastname: Hynes
authors.affiliation: Vaccine Testing Center, Department of Medicine, University of Vermont College of Medicine, Burlington, VT 05401, USA.
authors.forename: Catherine J
authors.initials: CJ
authors.lastname: Larsson
authors.affiliation: Center for Immunization Research, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA.
authors.forename: Beulah P
authors.initials: BP
authors.lastname: Sabundayo
authors.affiliation: Center for Immunization Research, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA.
authors.forename: Kawsar R
authors.initials: KR
authors.lastname: Talaat
authors.affiliation: Center for Immunization Research, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA.
authors.forename: Anna
authors.initials: A
authors.lastname: Janiak
authors.affiliation: Vaccine Testing Center, Department of Medicine, University of Vermont College of Medicine, Burlington, VT 05401, USA.
authors.forename: Marya P
authors.initials: MP
authors.lastname: Carmolli
authors.affiliation: Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors.forename: Catherine J
authors.initials: CJ
authors.lastname: Luke
authors.affiliation: Vaccine Testing Center, Department of Medicine, University of Vermont College of Medicine, Burlington, VT 05401, USA.
authors.forename: Sean A
authors.initials: SA
authors.lastname: Diehl
authors.affiliation: Center for Immunization Research, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA. adurbin1@jhu.edu.
authors.forename: Anna P
authors.initials: AP
authors.lastname: Durbin
mesh_terms: D000328:Adult; D003715:Dengue / Q000276:immunology* / Q000517:prevention & control*; D053059:Dengue Vaccines / Q000008:administration & dosage / Q000276:immunology*; D005260:Female; D006801:Humans; D008297:Male; D008954:Models, Biological; D014611:Vaccination; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000276:immunology*; D014766:Viremia / Q000276:immunology / Q000821:virology
chemical_list: D053059:Dengue Vaccines; D014613:Vaccines, Attenuated