Enhancing, controlling, and sterilizing dengue immunity and the development of broadly protective responses
Year: 2026
Type: preprint
Study design: Clinical Trial
Abstract: Dengue is the canonical viral disease for which immune history predicts protective versus pathogenic responses and immunogenicity. Yet, due to limitations in animal models and clinical presentation after peak viremia, how pre-infection and early immune responses affect dengue outcomes is not confirmed. We conducted a phase 1 clinical trial with 45 healthy adults to test if secondary infection challenge with a heterotypic, full-length, attenuated virus increases viremia and immunogenicity compared to primary and tertiary infection. Viremia was associated with more, but still mild, clinical signs and symptoms, and secondary infection predicted greater viremia and neutralizing antibodies. However, those with the highest baseline enhancing antibodies experienced delayed inflammatory and adaptive activation, the highest viremia, strong acute immune responses, but waning of potent CD8 + T cells and antibodies. Baseline antibodies to non-structural protein 1 of multiple serotypes predicted early interferon and balanced immune activation, viremia control, and development of enduring, potent B and T cells, revealing how vaccines can induce broad long-lasting protection. Finally, these antibody and T cell profiles at baseline predicted sterilization of infection. We demonstrate that controlled human challenge can delineate coordinated versus dysregulated acute responses and effects on immunogenicity, informing therapeutic and vaccine strategies for dengue and other viral diseases.
Source: medRxiv
Authors: Camila D. Odio, Rosemary A. Aogo, Saba Firdous, Charlie Voirin, Silvia Blanco-Rivera, Kelsey E. Lowman, Nhyira Asante, Ysabelle Broderson, Keerthi Konda, Chloe M. Hasund, Amparo Martinez-Perez, Patrick I. Mpingabo, Melissa Law, Caitlin Jarvis, Viviane Callier, Sally Hunsberger, Maria Abad Fernandez, Aravinda de Silva, Robbie Kattappuram, Gitanjali Bhushan, Christina Yek, Jessica Manning, Anna P. Durbin, Jeffrey I. Cohen, Daniela Weiskopf, Stephen S. Whitehead, Leah C. Katzelnick
Institutions: National Institutes of Health, National Institute of Allergy and Infectious Diseases, University of Cambridge, La Jolla Institute for Immunology, Frederick National Laboratory for Cancer Research, University of North Carolina at Chapel Hill, National Institutes of Health Clinical Center, Johns Hopkins University, University of California San Diego
Language: English
Field: Medicine
Domain: Health Sciences
Open Access status: green
Funder: National Institutes of Health
OpenAlex ID: W7141384530