Postbaccalaureate Fellow National Institute of Allergy and Infectious Diseases, National Institutes of Health, United States
Disclosure(s):
Keerthi Konda: No financial relationships to disclose
Introduction/Rationale: Pre-existing dengue immunity shapes subsequent immune responses, which can either be protective or pathogenic, though the underlying mechanisms remain poorly defined. Using a live attenuated monovalent DENV3 vaccine, we investigated how baseline immunity shapes cytokine, plasmablast, and clinical biomarker responses.
Methods: Participants were classified as naïve, heterotypic to a single serotype, or polytypic based on screening neutralizing antibodies, then restratified using area under the curve of viremia by qRT-PCR. We profiled 30 cytokines by Luminex and assessed plasmablast responses by ELISpot alongside standard clinical biomarkers.
Results: Low-viremia participants, most of whom had polytypic immunity, had early increases in innate cytokines, such as IL-6, IL-7, GM-CSF, and IFN-γ, followed by downregulated TNF-alpha and IL-2R and elevated MCP-1, lymphocyte, and monocyte counts, consistent with efficient viral control. The intermediate-viremia group showed early elevations in IFN-α and Th1-associated cytokines, followed by expansion of DENV3-reactive IgG⁺ and IgA⁺ plasmablasts, and IP-10 and IL1-RA induction, indicating a coordinated antiviral response with moderate inflammation. High-viremia participants, who mostly had heterotypic immunity, had more delayed increases in DENV-specific IgG⁺ plasmablasts and broader and more sustained elevations in proinflammatory and tissue-activating cytokines, such as G-CSF, VEG-F, and MIP-1 chemokines.
Conclusion: Pre-existing dengue immunity coupled with post-vaccine viremia delineates individuals into distinct profiles. We observed transient innate activation and controlled inflammation in low viremia participants, a coordinated adaptive response in the intermediate viremia group, and low-level but broad and persistent inflammation in the high viremia group. Understanding these profiles can help refine dengue interventions to improve safety and protective efficacy.
