Analysis of T Cell Immunity Generated by Takeda’s Tetravalent Dengue Vaccine

Abstract

Abstract Dengue is a viral disease transmitted to humans through the bite of infected mosquitoes and is caused by dengue virus (DENV), which has four distinct serotypes, DENV1 to DENV4. Severe dengue is a leading cause of serious illness and death in some Asian and Latin American countries. The Walter Reed Army Institute of Research (WRAIR) has been working to investigate the cell mediated immunogenicity of Takeda’s live attenuated virus tetravalent dengue vaccine (TAK-003). Previously, we have used ELISPOT and Flow-ICS assays to show that TAK-003 induces a robust IFN-γ producing DENV-specific T cell response that is durable to at least 6 months post-vaccination. In addition, this response is mediated by both CD8+ and CD4+ T cells that produce IFN-γ and/or TNFα and IL-2. Using samples from a phase II study, DEN-313 (NCT02948829) conducted in healthy children aged 4 to 16 years in dengue endemic locations, herewith we extend the findings on TAK-003 induced DENV-specific T cell responses to: (1) present data on durability of the CMI response through 3 years post-vaccination; (2) verify the serotype coverage of the T cell response; (3) assess multifunctional capacity of the durable memory T cells, and (4) describe the phenotypic changes that occur among these cells based upon central memory (CD45RA−/CCR7+), effector memory (CD45RA−/CCR7−) and effector memory RA phenotyping (CD45RA+/CCR7−). Our data describe the frequency, functionality, and memory phenotype of T cells induced by TAK-003 up to 3 years post vaccination. Finding received through corporative research and development agreement with Takeda vaccine company.