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TV005 dengue vaccine protects against dengue serotypes 2 and 3 in two controlled human infection studies.
Pierce, Kristen K; Durbin, Anna P; Walsh, Mary-Claire R; Carmolli, Marya; Sabundayo, Beulah P; Dickson, Dorothy M; Diehl, Sean A; Whitehead, Stephen S; Kirkpatrick, Beth D.
Afiliação
  • Pierce KK; Department of Medicine and.
  • Durbin AP; Department of Microbiology and Molecular Genetics, The University of Vermont Larner College of Medicine, Vaccine Testing Center, Burlington, Vermont, USA.
  • Walsh MR; The Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.
  • Carmolli M; Department of Medicine and.
  • Sabundayo BP; Department of Microbiology and Molecular Genetics, The University of Vermont Larner College of Medicine, Vaccine Testing Center, Burlington, Vermont, USA.
  • Dickson DM; Department of Microbiology and Molecular Genetics, The University of Vermont Larner College of Medicine, Vaccine Testing Center, Burlington, Vermont, USA.
  • Diehl SA; The Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.
  • Whitehead SS; Department of Microbiology and Molecular Genetics, The University of Vermont Larner College of Medicine, Vaccine Testing Center, Burlington, Vermont, USA.
  • Kirkpatrick BD; Department of Microbiology and Molecular Genetics, The University of Vermont Larner College of Medicine, Vaccine Testing Center, Burlington, Vermont, USA.
J Clin Invest ; 134(3)2024 Feb 01.
Article em En | MEDLINE | ID: mdl-37971871
BACKGROUNDDisease due to dengue viruses is a growing global health threat, causing 100-400 million cases annually. An ideal dengue vaccine should demonstrate durable protection against all 4 serotypes in phase III efficacy trials, however the lack of circulating serotypes may lead to incomplete efficacy data. Controlled human infection models help downselect vaccine candidates and supply critical data to supplement efficacy trials. We evaluated the efficacy of a leading live-attenuated tetravalent dengue vaccine candidate, TV005, against infection with a newly established dengue serotype 3 or an established serotype 2 challenge virus.METHODSTwo randomized, controlled clinical trials were performed. In study 1, a total of 42 participants received TV005 or placebo (n = 21 each), and 6 months later, all were challenged with dengue 2 virus (rDEN2Δ30) at a dose of 103 PFU. In study 2, a total of 23 participants received TV005 and 20 received placebo, and 6 months later, all were challenged with 104 PFU dengue 3 virus (rDEN3Δ30). The study participants were closely monitored for safety, viremia, and immunologic responses. Infection, measured by post-challenge viremia, and the occurrence of rash and neutropenia were the primary endpoints. Secondary endpoints included safety, immunologic, and virologic profiles following vaccination with TV005 and subsequent challenge with the rDEN2Δ30 or rDEN3Δ30 strain.RESULTSTV005 was well tolerated and protected all vaccinated volunteers from viremia with DENV2 or DENV3 (none infected in either group). Placebo recipients had post-challenge viremia (100% in study 1, 85% in study 2), and all experienced rash following challenge with either serotype.CONCLUSIONSTV005 is a leading tetravalent dengue vaccine candidate that fully protected against infection with DENV2 and DENV3 in an established controlled human infection model.TRIAL REGISTRATIONClinicalTrials.gov NCT02317900 and NCT02873260.FUNDINGIntramural Research Program, NIH (contract HHSN272200900010C).
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Dengue / Vírus da Dengue / Exantema / Vacinas contra Dengue Limite: Humans Idioma: En Ano de publicação: 2024 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Dengue / Vírus da Dengue / Exantema / Vacinas contra Dengue Limite: Humans Idioma: En Ano de publicação: 2024 Tipo de documento: Article