A recombinant, chimeric tetravalent dengue vaccine candidate based on a dengue virus serotype 2 backbone

ABSTRACT

Dengue fever is caused by infection with one of four dengue virus (DENV) serotypes (DENV-1–4), necessitating tetravalent dengue vaccines that can induce protection against all four DENV. Takeda’s live attenuated tetravalent dengue vaccine candidate (TDV) comprises an attenuated DENV-2 strain plus chimeric viruses containing the prM and E genes of DENV-1, -3 and -4 cloned into the attenuated DENV-2 ‘backbone’. In Phase 1 and 2 studies, TDV was well tolerated by children and adults aged 1.5–45 years, irrespective of prior dengue exposure; mild injection-site symptoms were the most common adverse events. TDV induced neutralizing antibody responses and seroconversion to all four DENV as well as cross-reactive T cell-mediated responses that may be necessary for broad protection against dengue fever.

KEYWORDS:

• Dengue
• live attenuated tetravalent vaccine
• TDV development
• safety
• clinical immunology
• dengue-seropositive participants
• dengue-endemic

Financial & competing interests disclosure

The studies described in this review were funded by Inviragen and Takeda Vaccines, Inc. J Osorio and D Stinchcomb were employed by Inviragen at the time the reviewed studies were carried out, and are currently Senior Scientific Advisors to Takeda Vaccines, Inc. D Wallace is an employee of Takeda Vaccines, Inc. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. Editorial assistance with preparation of the manuscript was provided by Samantha Santangelo, PhD, funded by Takeda Vaccines Inc.