11 décembre 2025: Pre Eva Harris
12H30
CMU - Auditoire Renold
suivi d'un apéritif
Hôte: Pre Isabella ECKERLE
Centre des maladies virales émergentes UNIGE-HUG
Département de médecine, Faculté de médecine UNIGE & HUG
Pre Eva Harris
Professor and Chair, Division of Infectious Diseases and Vaccinology
Director, Center for Global Public Health
School of Public Health, University of California, Berkeley
«The increasing Complexity of Flavivirus Epidemiology and Immunology: Insights from a Nicaraguan Cohort Study»
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.
Biography
Dr. Eva Harris is a Professor and Chair of the Division of Infectious Diseases and Vaccinology, Professor in the Department of Molecular and Cell Biology, Chair of the Infectious Diseases and Immunity PhD Program, and Director of the Center for Global Public Health, in the School of Public Health at the University of California, Berkeley, and President of the Sustainable Sciences Institute. She has developed a multidisciplinary approach to study the molecular virology, pathogenesis, immunology, epidemiology, clinical aspects and control of dengue, Zika and chikungunya, the most prevalent mosquito-borne viral diseases in humans. Her work addresses immune correlates of protection and pathogenesis and viral and host factors that modulate disease severity, using in vitro approaches, animal models, and research involving human populations. One research major focus is on studies of arboviral disease in humans, including antibody and B cell responses and correlates of protection, diagnostics and seroprevalence studies, and viral evolution. Another focus is viral pathogenesis, specifically the role of flavivirus NS1 protein, Crimean Congo hemorrhagic fever virus GP38 protein, and other viral toxins in vascular leak and virus dissemination. Her international work includes laboratory-based and epidemiological studies of arboviral diseases in endemic Latin American countries, particularly in Nicaragua through close collaborations for over 35 years. Ongoing long-term projects in Nicaragua include a 25-year hospital-based study of severe arboviral disease, a unique 21-year pediatric cohort study, and household transmission studies of dengue, Zika, and chikungunya in Managua. Dr. Harris has published over 385 peer-reviewed articles, as well as a book on her international scientific work. In 1998, she and like-minded colleagues founded the non-profit organization Sustainable Sciences Institute, with offices in Oakland and Nicaragua, to build scientific capacity in LMIC to address public health and infectious disease issues.
6 nov. 2025