Protection against symptomatic dengue infection by neutralizing antibodies varies by infection history and infecting serotype

Sandra Bos (), Aaron L. Graber, Jaime A. Cardona-Ospina, Elias M. Duarte, Jose Victor Zambrana, Jorge A. Ruíz Salinas, Reinaldo Mercado-Hernandez, Tulika Singh, Leah C. Katzelnick, Aravinda Silva, Guillermina Kuan, Angel Balmaseda and Eva Harris ()
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Sandra Bos: University of California, Berkeley
Aaron L. Graber: University of California, Berkeley
Jaime A. Cardona-Ospina: University of California, Berkeley
Elias M. Duarte: University of California, Berkeley
Jose Victor Zambrana: Sustainable Sciences Institute
Jorge A. Ruíz Salinas: Sustainable Sciences Institute
Reinaldo Mercado-Hernandez: University of California, Berkeley
Tulika Singh: University of California, Berkeley
Leah C. Katzelnick: National Institute of Allergy and Infectious Diseases, National Institutes of Health
Aravinda Silva: University of North Carolina
Guillermina Kuan: Sustainable Sciences Institute
Angel Balmaseda: Sustainable Sciences Institute
Eva Harris: University of California, Berkeley

Nature Communications, 2024, vol. 15, issue 1, 1-13

Abstract: Abstract Dengue viruses (DENV1–4) are the most prevalent arboviruses in humans and a major public health concern. Understanding immune mechanisms that modulate DENV infection outcome is critical for vaccine development. Neutralizing antibodies (nAbs) are an essential component of the protective immune response, yet their measurement often relies on a single cellular substrate and partially mature virions, which does not capture the full breadth of neutralizing activity and may lead to biased estimations of nAb potency. Here, we analyze 125 samples collected after one or more DENV infections but prior to subsequent symptomatic or inapparent DENV1, DENV2, or DENV3 infections from a long-standing pediatric cohort study in Nicaragua. By assessing nAb responses using Vero cells with or without DC-SIGN and with mature or partially mature virions, we find that nAb potency and the protective NT50 cutoff are greatly influenced by cell substrate and virion maturation state. Additionally, the correlation between nAb titer and protection from disease depends on prior infection history and infecting serotype. Finally, we uncover variations in nAb composition that contribute to protection from symptomatic infection differently after primary and secondary prior infection. These findings have important implications for identifying antibody correlates of protection for vaccines and natural infections.

Date: 2024
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DOI: 10.1038/s41467-023-44330-8

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