Dengue-specific T cell immunity influenced by various levels of pre-existing immunity 2267557

Abstract

Abstract Introduction Dengue virus (DENV) is a mosquito-borne flavivirus responsible for significant global morbidity and mortality. Prior exposure to different DENV serotypes can shape subsequent immune responses and influence both protection and risk. This challenges the development of a universally effective and safe dengue vaccine, capable of inducing balanced and durable immunity against all four serotypes. T cells constitute a critical arm of dengue immunity, acting independently of antibodies. In this work, we have evaluated the dengue-specific T-cell responses elicited by an attenuated monovalent DENV3 vaccine in participants with various levels of pre-existing DENV exposure. Methods Peripheral blood mononuclear cells (PBMCs) from vaccine recipients of different dengue serostatus (seronegative, monotypic, and multitypic-exposure) were stimulated with experimentally defined DENV3 epitope megapools for DENV structural and nonstructural epitopes. We profiled T cell activation markers, memory phenotypes, and cytokine secretion using a panel of 30+ markers in high-parameter flow cytometry. Results T cells responses were analyzed longitudinally pre-vaccination, and 15, 28 and 90 days after vaccination. The DENV-3 challenge induced measurable DENV-specific T-cell responses for both structural and non-structural components. We observed individual variability in T cell responses that are influenced by their baseline serostatus and viremia burden. Conclusion Our study provides valuable insights into the factors shaping cellular immunity to a novel DENV challenge Funding Source 2P01AI106695-11 Topic Categories Viral Immunology (VIR)