2025 – Neelika Malavige

Title:
Characterization of T cell responses in obese and non-obese dengue patients with varying disease severity

Abstract:
Those with obesity and associated metabolic diseases are at higher risk of developing severe dengue/dengue haemorrhagic fever (DHF). To further understand the potential differences in T cell responses in patients with varying severity of acute dengue and metabolic status, we assessed the functionality of DENV-specific T cell responses using peptides specific to 109 CD8+ and 90 CD4+ T cell epitopes identified from all four DENV serotypes, phenotypes of CD4+ and CD8+ T cell subsets in patients with varying severity of disease severity and obesity.

The magnitude of the DENV-specific IFNγ T cell responses measured by ex vivo IFNγ ELISpot assays to both CD4+ and CD8+ peptide pools, increased significantly from the first time point (≤4 days since onset of illness), to the second time point (5-7 days since onset of illness), in patients with DF (p<0.0001) but not with DHF. A significant increase in the magnitude of DENV-specific IFNγ T cell responses were also seen in lean patients (p=0.0002), but not in obese patients. Although adiponectin levels during early illness correlated with the frequency of ex vivo DENV-specific IFNγ producing T cells at the second time point in patients with DF, the adiponectin levels inversely correlated with IFNγ producing T cells in patients with DHF.

Cutaneous lymphocyte associated antigen (CLA) expression was significantly higher in the CD8+ T cell subset in patients with DF and DHF compared to healthy controls (HC) and these differences were most significant in CD8+CD45RA- T cells. CLA expression was also the highest in the CD8+CD45RA- of obese individuals, which was significantly higher compared to lean individuals (p=0.01). CD27 and CD127 were both significantly downregulated in patients with DHF compared to DF, with ICOS expression being significantly higher in CD8+ T cells in DHF, suggesting impaired functionality and phenotypic characteristic, especially in obese patients could contribute to disease pathogenesis.

Biography:
Neelika Malavige is a Professor at the Department of Immunology and Molecular Medicine, University of Sri Jayewardenepura and an academic visitor at the Weatherall Institute of Molecular Medicine, University of Oxford. She is also the president elect of the International Society of Infectious Disease. Her research focused on immunopathogenesis of dengue, biomarkers and immune correlates of protection and translating these findings into clinical trials. She sits on or chairs numerous national and international scientific advisory boards, funding panels and editorial boards.