«The increasing Complexity of Flavivirus Epidemiology and Immunology: Insights from a Nicaraguan Cohort Study»

11.12.2025 12:30 – 13:30

Dengue (DENV) and Zika (ZIKV) viruses, closely related mosquito-borne flaviviruses, present significant public health and vaccine development challenges due to their complex immune interactions. Responsible for hundreds of millions of infections worldwide every year, flaviviruses continue to increase in case numbers and geographic reach, with recent expansion into Europe and the US. Leveraging our long-term arboviral cohort study in Nicaragua, currently in its 21st consecutive year, we explore the immunological basis of clinical and epidemiological observations. Specifically, we find that prior ZIKV infection is a risk factor for severe disease in a subsequent DENV2 infection due to 1) cross-reactive IgA antibodies to DENV2 nonstructural protein 1 that activate neutrophil degranulation during the acute phase of disease and 2) skewing of the memory B cell response such that upon DENV2 infection, the predominant clone recalled from prior ZIKV infection fails to neutralize DENV2. Finally, we show how imprinting also affects the outcome of a third sequential flavivirus infection by modulating the magnitude and quality of neutralizing antibodies, demonstrating that the order of virus infection matters as DENV followed by ZIKV is a risk for subsequent symptomatic and severe DENV disease whereas ZIKV followed by DENV is not. Overall, these findings have significant implications for vaccine development strategies and pandemic preparedness, underscoring the importance of considering prior flavivirus exposure history.

Lieu

Bâtiment: CMU

Auditoire Renold

entrée libre

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afficheA3_FIB_Harris.pdf

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