Immune Cell Phenotypes that Determine Disease Severity and Long-Term Neutralizing Antibody Titers after Natural Dengue Virus Infection

Abstract

Prior immunological exposure to dengue virus can be both protective and disease-enhancing during subsequent infections with different dengue virus serotypes. We provide here for the first time a systematic, longitudinal analysis of B cell, T cell, and antibody responses in the same patients. Antibody responses as well as T and B cell activation differentiated primary versus secondary responses. Disease severity was associated with lower frequencies of activated, terminally differentiated T cells and higher percentages of effector memory CD4 T cells. Patients with more severe disease tended to have higher percentages of plasmablasts. This did not translate into long-term antibody titers, since neutralizing titers after six months were associated with percentages of specific memory B cells but not with acute plasmablast activation. Overall, our unbiased analysis reveals novel and unexpected associations between cellular profiles and disease severity,opening new opportunities to study immunopathology in dengue disease and potential predictive value of these parameters.

Keywords: Dengue, T cell, B cell, Longitudinal, Disease Severity, Antibodies, Correlates of Protection