The live attenuated dengue vaccine TV003 elicits complete protection against dengue in a human challenge model

Beth D. Kirkpatrick, Stephen S. Whitehead, Kristen K. Pierce, Cecilia M. Tibery, Palmtama L. Grier, Noreen A Hynes, Catherine J. Larsson, Beulah Perdue Sabundayo, Kawsar Rasmy Talaat, Anna Janiak, Marya P. Carmolli, Catherine J. Luke, Sean A. Diehl, Anna P Durbin

Research output: Contribution to journalArticle

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, rDEN2D30, was conducted. The primary endpoint of the trial was protection against dengue infection, defined as rDEN2D30 viremia. Secondary endpoints were protection against rash and neutropenia. All 21 recipients of TV003 who were challenged with rDEN2D30 were protected from infection with rDEN2D30. None developed viremia, rash, or neutropenia after challenge. In contrast, 100% of the 20 placebo recipients who were challenged with rDEN2D30 developed viremia, 80% developed rash, and 20% developed neutropenia. TV003 induced complete protection against challenge with rDEN2D30 administered 6months 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.

Original languageEnglish (US)
Article number330RA36
JournalScience Translational Medicine
Volume8
Issue number330
DOIs
StatePublished - Mar 16 2016

ASJC Scopus subject areas

  • Medicine(all)

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    Kirkpatrick, B. D., Whitehead, S. S., Pierce, K. K., Tibery, C. M., Grier, P. L., Hynes, N. A., Larsson, C. J., Sabundayo, B. P., Talaat, K. R., Janiak, A., Carmolli, M. P., Luke, C. J., Diehl, S. A., & Durbin, A. P. (2016). The live attenuated dengue vaccine TV003 elicits complete protection against dengue in a human challenge model. Science Translational Medicine, 8(330), [330RA36]. https://doi.org/10.1126/scitranslmed.aaf1517