title: 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.
authors.affiliation: a Department of Pathobiological Sciences, School of Veterinary Medicine , University of Wisconsin-Madison , Madison , WI , US.
authors.forename: Jorge E
authors.initials: JE
authors.lastname: Osorio
authors.affiliation: b Clinical Development , Takeda Vaccines Pte. Ltd , Singapore , Singapore.
authors.forename: Derek
authors.initials: D
authors.lastname: Wallace
authors.affiliation: c Scientific Affairs and Policy , Takeda Vaccines, Inc ., Deerfield , IL , US.
authors.forename: Dan T
authors.initials: DT
authors.lastname: Stinchcomb
mesh_terms: D057134:Antibodies, Neutralizing / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood; D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D003715:Dengue / Q000276:immunology / Q000517:prevention & control*; D053059:Dengue Vaccines / Q000009:adverse effects / Q000235:genetics / Q000276:immunology*; D003716:Dengue Virus / Q000235:genetics / Q000276:immunology*; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology / Q000473:pathology; D006801:Humans; D065288:Serogroup; D013601:T-Lymphocytes / Q000276:immunology; D016896:Treatment Outcome; D014613:Vaccines, Attenuated / Q000009:adverse effects / Q000235:genetics / Q000276:immunology; D014614:Vaccines, Synthetic / Q000009:adverse effects / Q000235:genetics / Q000276:immunology; D014759:Viral Envelope Proteins / Q000235:genetics / Q000276:immunology
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D053059:Dengue Vaccines; D014613:Vaccines, Attenuated; D014614:Vaccines, Synthetic; D014759:Viral Envelope Proteins; C074932:prM protein, Flavivirus
keywords: Dengue; TDV development; clinical immunology; dengue-endemic; dengue-seropositive participants; live attenuated tetravalent vaccine; safety