Ruchira Khosavanna, MD
Nominated From: University of Washington & Yale University
Research Site: Chulalongkorn University
Research Area: Orthoflavivirus, Dengue virus, Cross-reactive immunity
Primary Mentor: Dr. Albert Ko
Research Project
Delineating Cross-Reactive T Cell Responses to Zika Virus in a Dengue Hyperendemic Area: A Prospective Study in a Multi-Generational Cohort in Kamphaeng Phet, Thailand
Dengue virus (DENV) and Zika virus (ZIKV) are closely related orthoflaviviruses, both transmitted by Aedes aegypti and Aedes albopictus mosquitoes, that cocirculate in many regions and share considerable structural and genomic similarity. Together, they pose a significant public health threat, particularly in lower- and middle-income countries. While their antigenic overlap is known to elicit highly cross-reactive humoral immune responses, much less is understood about the nature and determinants of cross-reactive cell-mediated immunity (CMI) between these viruses. This gap in knowledge is important given cross-reactive T cell responses may influence either protection or immunopathology during sequential flavivirus infections, with implications for vaccine development and public health preparedness. This study aims to characterize the magnitude and determinants of cross-reactive T cell responses to ZIKV in individuals with prior DENV infection, using a novel whole blood-based cytokine release assay (CRA) in Kamphaeng Phet, Thailand — a dengue hyperendemic region with a well-established, longitudinal, multi-generational cohort. The study will address the presence of cross-reactive T cell responses to ZIKV in individuals with prior DENV infection, assess how infecting DENV serotype influences the magnitude of these responses, and evaluate the impact of time since DENV infection on cross-reactive T cell immunity.
Research Significance
By elucidating the dynamics of flavivirus-specific T cell immunity in a real-world endemic setting, this study will provide insights into how pre-existing DENV immunity shapes ZIKV-specific cellular immune responses. It will lay the groundwork for further investigations into interactions between flaviviruses and their modulation of host immunity and disease outcomes. Ultimately, these findings have the potential to inform the development of next generation flavivirus vaccines and improve preparedness for the clinical and epidemiologic consequences of sequential flavivirus infections in vulnerable populations.
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