Role of acute B cell response in dengue disease severity and long-term immunity (67.19)

Abstract

Abstract The four serotypes of dengue virus (DENV) cause dengue fever (DF) and dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS), the most prevalent mosquito-borne viral disease in humans. Little is known about the acute B cell response during DENV infection and its impact on the breadth and quality of the long-term humoral response. We have measured by flow cytometry the percent of naïve, memory B cells and plasmablasts (PB)/plasma cells (PC) in fresh whole blood from acutely infected patients from a hospital-based study in Managua, Nicaragua. DENV-positive cases demonstrate a significant increase in PB/PCs as compared to DENV-negative cases. The percent of PB/PC in DENV-negative samples ranges from 0.004-5.44% (mean 0.6 +/- 0.19; n=40) compared to 0.04-7.68% (mean 1.5 +/- 0.21; n=83) in DENV-positive samples (p=0.003). No significant difference was found among naïve and memory B cell compartments. Serum avidity is greater in secondary as compared to primary DENV infections. The percent of PB/PC at day 5 post-onset of symptoms appears to positively correlate with serum avidity as measured by ELISA at convalescence (r2=0.83, p=0.015). These data will be correlated with the number of DENV-specific Ab-secreting cells (ASC) measured by ELISpot, as well as with disease severity and the DENV-specific neutralization capacities of the serum. This study will set the basis for future studies and could ultimately impact the design of safe and effective dengue vaccines.