Characterization of the cell-mediated immune response to the NIH tetravalent dengue vaccine in an endemic population

Abstract

Dengue is now endemic in more than 100 countries, with Southeast Asian and Pacific Island regions being the most seriously affected. The Department of Defense has long recognized the threat of dengue and has made great contributions to understanding it. The ideal dengue vaccine will provide long-lasting protection against all four serotypes of dengue virus (DENV1-4) and will be effective in both endemic and non-endemic populations. Several tetravalent dengue vaccines are either licensed or in advanced stages of clinical development, including the live attenuated vaccine candidate developed by the NIH. The purpose of this study is to characterize the cellular immune responses to the NIH vaccine, with particular attention to the activation and memory profiles of DENV-specific T and B cell populations. Our hypothesis is that the NIH vaccine induces a durable and tetravalent DENV-specific adaptive immune response, which varies in its magnitude and phenotype over time (3 years post-vaccination) and across age strata. To assess the magnitude, breadth, and evolution of DENV-specific T and B cells following vaccination, we use a suite of different assays, including IFNγ ELISpot, memory B cell fluorospot, and flow cytometry-based assays. This study evaluates the ability of the NIH vaccine to induce durable and balanced immune responses to all four DENV serotypes, and how that compares to naturally acquired immunity.